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Conserved domains on  [gi|1233055010|ref|NP_001341549|]
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DNA mismatch repair protein Mlh1 isoform 2 [Homo sapiens]

Protein Classification

MutL_Trans_MLH1 and Mlh1_C domain-containing protein( domain architecture ID 13511996)

protein containing domains HATPase, MutL_Trans_MLH1, and Mlh1_C

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Mlh1_C pfam16413
DNA mismatch repair protein Mlh1 C-terminus; This is the C-terminal domain of DNA mismatch ...
 404-658 3.48e-135

DNA mismatch repair protein Mlh1 C-terminus; This is the C-terminal domain of DNA mismatch repair protein Mlh1, these proteins belong to the MutL family. This domain forms part of the endonuclease active site.


:

Pssm-ID: 465109  Cd Length: 260  Bit Score: 396.52  E-value: 3.48e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 404 NLTSVLSLQEEINEQGHEVLREMLHNHSFVGCVNPQ--WALAQHQTKLYLLNTTKLSEELFYQILIYDFANFGVLRLSEP 481
Cdd:pfam16413   1 RLTSIKELRAEVEESMHKELTEIFANHTFVGCVDERrrLALIQHGTKLYLVDYGALSEELFYQIGLTDFGNFGRIRLSPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 482 APLFDLAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAEMLADYFSLEIDEEGNLIGLPLLIDNYVPPLEGLPIFILR 561
Cdd:pfam16413  81 LSLYELLELALESEESGWTEEDGPKEELAEKIVELLIEKAEMLEEYFSIEIDEDGNLESLPLLLKGYTPNLDKLPLFLLR 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 562 LATEVNWDEEKECFESLSKECAMFYSIRKQY----ISEESTLSGQQSEVPGSIPNSWKWTVEHIVYKALRSHILPPKHFT 637
Cdd:pfam16413 161 LATEVDWDDEKECFETFLRELALFYSPEPLPppsnDESNDDEDEEEDEEIEARREEWKWVIEHVLFPAIKRRLLPPKSLL 240

                         250       260
                  ....*....|....*....|.
gi 1233055010 638 EDGnILQLANLPDLYKVFERC 658
Cdd:pfam16413 241 KDT-VVQVANLPDLYKVFERC 260
mutl super family cl36694
DNA mismatch repair protein MutL; All proteins in this family for which the functions are ...
 4-217 1.87e-80

DNA mismatch repair protein MutL; All proteins in this family for which the functions are known are involved in the process of generalized mismatch repair. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


The actual alignment was detected with superfamily member TIGR00585:

Pssm-ID: 273155 [Multi-domain]  Cd Length: 312  Bit Score: 257.57  E-value: 1.87e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010   4 EALASISHVAHVTITTKT-ADGKCAYRASYsDGKLKAPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVV 82
Cdd:TIGR00585  97 EALASISSVSRLTITTKTsAADGLAYQALL-EGGMIESIKPAPRPVGTTVEVRDLFYNLPVRRKFLKSPKKEFRKILDVL 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010  83 GRYSVHNAGISFSVKKQGETVADVRTLPNASTVDN-IRSIFGNAVSRELIEIGcEDKTLAFKMNGYISNANYSVKKCI-- 159
Cdd:TIGR00585 176 QRYALIHPDISFSLTHDGKKVLQLSTKPNQSTKENrIRSVFGTAVLRKLIPLD-EWEDLDLQLEGFISQPNVTRSRRSgw 254

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1233055010 160 FLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVH 217
Cdd:TIGR00585 255 QFLFINGRPVELKLLLKAIREVYHEYLPKGQYPVFVLNLEIDPELVDVNVHPDKKEVR 312
 
Name Accession Description Interval E-value
Mlh1_C pfam16413
DNA mismatch repair protein Mlh1 C-terminus; This is the C-terminal domain of DNA mismatch ...
 404-658 3.48e-135

DNA mismatch repair protein Mlh1 C-terminus; This is the C-terminal domain of DNA mismatch repair protein Mlh1, these proteins belong to the MutL family. This domain forms part of the endonuclease active site.


Pssm-ID: 465109  Cd Length: 260  Bit Score: 396.52  E-value: 3.48e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 404 NLTSVLSLQEEINEQGHEVLREMLHNHSFVGCVNPQ--WALAQHQTKLYLLNTTKLSEELFYQILIYDFANFGVLRLSEP 481
Cdd:pfam16413   1 RLTSIKELRAEVEESMHKELTEIFANHTFVGCVDERrrLALIQHGTKLYLVDYGALSEELFYQIGLTDFGNFGRIRLSPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 482 APLFDLAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAEMLADYFSLEIDEEGNLIGLPLLIDNYVPPLEGLPIFILR 561
Cdd:pfam16413  81 LSLYELLELALESEESGWTEEDGPKEELAEKIVELLIEKAEMLEEYFSIEIDEDGNLESLPLLLKGYTPNLDKLPLFLLR 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 562 LATEVNWDEEKECFESLSKECAMFYSIRKQY----ISEESTLSGQQSEVPGSIPNSWKWTVEHIVYKALRSHILPPKHFT 637
Cdd:pfam16413 161 LATEVDWDDEKECFETFLRELALFYSPEPLPppsnDESNDDEDEEEDEEIEARREEWKWVIEHVLFPAIKRRLLPPKSLL 240

                         250       260
                  ....*....|....*....|.
gi 1233055010 638 EDGnILQLANLPDLYKVFERC 658
Cdd:pfam16413 241 KDT-VVQVANLPDLYKVFERC 260
mutl TIGR00585
DNA mismatch repair protein MutL; All proteins in this family for which the functions are ...
 4-217 1.87e-80

DNA mismatch repair protein MutL; All proteins in this family for which the functions are known are involved in the process of generalized mismatch repair. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 273155 [Multi-domain]  Cd Length: 312  Bit Score: 257.57  E-value: 1.87e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010   4 EALASISHVAHVTITTKT-ADGKCAYRASYsDGKLKAPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVV 82
Cdd:TIGR00585  97 EALASISSVSRLTITTKTsAADGLAYQALL-EGGMIESIKPAPRPVGTTVEVRDLFYNLPVRRKFLKSPKKEFRKILDVL 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010  83 GRYSVHNAGISFSVKKQGETVADVRTLPNASTVDN-IRSIFGNAVSRELIEIGcEDKTLAFKMNGYISNANYSVKKCI-- 159
Cdd:TIGR00585 176 QRYALIHPDISFSLTHDGKKVLQLSTKPNQSTKENrIRSVFGTAVLRKLIPLD-EWEDLDLQLEGFISQPNVTRSRRSgw 254

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1233055010 160 FLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVH 217
Cdd:TIGR00585 255 QFLFINGRPVELKLLLKAIREVYHEYLPKGQYPVFVLNLEIDPELVDVNVHPDKKEVR 312
MutL_Trans_MLH1 cd03483
MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in ...
 113-237 5.48e-75

MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from ATP-binding site to the DNA breakage/reunion regions of the enzymes. MLH1 forms heterodimers with PMS2, PMS1 and MLH3. These three complexes have distinct functions in meiosis. hMLH1-hPMS2 also participates in the repair of all DNA mismatch repair (MMR) substrates. Roles for hMLH1-hPMS1 or hMLH1-hMLH3 in MMR have not been established. Cells lacking hMLH1 have a strong mutator phenotype and display microsatellite instability (MSI). Mutation in hMLH1 causes predisposition to HNPCC, Muir-Torre syndrome and Turcot syndrome (HNPCC variant). Mutation in hMLH1 accounts for a large fraction of HNPCC families.


Pssm-ID: 239565 [Multi-domain]  Cd Length: 127  Bit Score: 236.36  E-value: 5.48e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 113 STVDNIRSIFGNAVSRELIEIGCEDKT--LAFKMNGYISNANYSVKKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNT 190
Cdd:cd03483     1 STKDNIRSVYGAAVANELIEVEISDDDddLGFKVKGLISNANYSKKKIIFILFINNRLVECSALRRAIENVYANYLPKGA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1233055010 191 HPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKLL 237
Cdd:cd03483    81 HPFVYLSLEIPPENVDVNVHPTKREVHFLNEEEIIERIQKLVEDKLS 127
MutL COG0323
DNA mismatch repair ATPase MutL [Replication, recombination and repair];
4-239 2.12e-63

DNA mismatch repair ATPase MutL [Replication, recombination and repair];


Pssm-ID: 440092 [Multi-domain]  Cd Length: 515  Bit Score: 218.76  E-value: 2.12e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010   4 EALASISHVAHVTITTKTADGKCAYRASYSDGKLKaPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVVG 83
Cdd:COG0323    98 EALASIASVSRLTLTTRTAGAELGTRIEVEGGKVV-EVEPAAAPKGTTVEVRDLFFNTPARRKFLKSDATELAHITDVVR 176

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010  84 RYSVHNAGISFSVKKQGETVadVRTLPNASTVDNIRSIFGNAVSRELIEIgcEDKTLAFKMNGYISNANY--SVKKCIFL 161
Cdd:COG0323   177 RLALAHPDIAFTLIHNGREV--FQLPGAGDLLQRIAAIYGREFAENLLPV--EAEREGLRLSGYIGKPEFsrSNRDYQYF 252

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1233055010 162 lFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKLLGS 239
Cdd:COG0323   253 -FVNGRPVRDKLLSHAVREAYRDLLPKGRYPVAVLFLELDPELVDVNVHPTKTEVRFRDEREVYDLVRSAVREALAQA 329
mutL PRK00095
DNA mismatch repair endonuclease MutL;
4-329 2.12e-57

DNA mismatch repair endonuclease MutL;


Pssm-ID: 234630 [Multi-domain]  Cd Length: 617  Bit Score: 204.68  E-value: 2.12e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010   4 EALASISHVAHVTITTKTADGKCAYRASYSDGKLKaPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVVG 83
Cdd:PRK00095   97 EALPSIASVSRLTLTSRTADAAEGWQIVYEGGEIV-EVKPAAHPVGTTIEVRDLFFNTPARRKFLKSEKTELGHIDDVVN 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010  84 RYSVHNAGISFSVKKQGETVadVRTLPNASTVDNIRSIFGNAVSRELIEIGCEDktLAFKMNGYI-------SNANYsvk 156
Cdd:PRK00095  176 RLALAHPDVAFTLTHNGKLV--LQTRGAGQLLQRLAAILGREFAENALPIDAEH--GDLRLSGYVglptlsrANRDY--- 248

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 157 kcIFLlFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKL 236
Cdd:PRK00095  249 --QYL-FVNGRYVRDKLLNHAIRQAYHDLLPRGRYPAFVLFLELDPHQVDVNVHPAKHEVRFRDERLVHDLIVQAIQEAL 325

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 237 LGSN----------------SSRMYFTQTLLPGLAGPSGEMVKSTTSLTSSSTSGSSDKVYAHQMVRTDSREQKLDAFLQ 300
Cdd:PRK00095  326 AQSGlipaaaganqvlepaePEPLPLQQTPLYASGSSPPASSPSSAPPEQSEESQEESSAEKNPLQPNASQSEAAAAASA 405

                         330       340       350
                  ....*....|....*....|....*....|.
gi 1233055010 301 PLSK--PLSSQPQAIVTEDKTDISSGRARQQ 329
Cdd:PRK00095  406 EAAAaaPAAAPEPAEAAEEADSFPLGYALGQ 436
DNA_mis_repair pfam01119
DNA mismatch repair protein, C-terminal domain; This family represents the C-terminal domain ...
 119-236 4.16e-42

DNA mismatch repair protein, C-terminal domain; This family represents the C-terminal domain of the mutL/hexB/PMS1 family. This domain has a ribosomal S5 domain 2-like fold.


Pssm-ID: 426060 [Multi-domain]  Cd Length: 117  Bit Score: 148.03  E-value: 4.16e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 119 RSIFGNAVSRELIEIGCEDKTlaFKMNGYISNANYS-VKKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLS 197
Cdd:pfam01119   1 AAIYGKEFAENLLPIEKEDDG--LRLSGYISKPTLSrSNRDYQYLFVNGRPVRDKLLSHAIREAYRDLLPKGRYPVAVLF 78

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1233055010 198 LEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKL 236
Cdd:pfam01119  79 LEIDPELVDVNVHPTKREVRFRDEREVYDFIKEALREAL 117
 
Name Accession Description Interval E-value
Mlh1_C pfam16413
DNA mismatch repair protein Mlh1 C-terminus; This is the C-terminal domain of DNA mismatch ...
 404-658 3.48e-135

DNA mismatch repair protein Mlh1 C-terminus; This is the C-terminal domain of DNA mismatch repair protein Mlh1, these proteins belong to the MutL family. This domain forms part of the endonuclease active site.


Pssm-ID: 465109  Cd Length: 260  Bit Score: 396.52  E-value: 3.48e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 404 NLTSVLSLQEEINEQGHEVLREMLHNHSFVGCVNPQ--WALAQHQTKLYLLNTTKLSEELFYQILIYDFANFGVLRLSEP 481
Cdd:pfam16413   1 RLTSIKELRAEVEESMHKELTEIFANHTFVGCVDERrrLALIQHGTKLYLVDYGALSEELFYQIGLTDFGNFGRIRLSPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 482 APLFDLAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAEMLADYFSLEIDEEGNLIGLPLLIDNYVPPLEGLPIFILR 561
Cdd:pfam16413  81 LSLYELLELALESEESGWTEEDGPKEELAEKIVELLIEKAEMLEEYFSIEIDEDGNLESLPLLLKGYTPNLDKLPLFLLR 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 562 LATEVNWDEEKECFESLSKECAMFYSIRKQY----ISEESTLSGQQSEVPGSIPNSWKWTVEHIVYKALRSHILPPKHFT 637
Cdd:pfam16413 161 LATEVDWDDEKECFETFLRELALFYSPEPLPppsnDESNDDEDEEEDEEIEARREEWKWVIEHVLFPAIKRRLLPPKSLL 240

                         250       260
                  ....*....|....*....|.
gi 1233055010 638 EDGnILQLANLPDLYKVFERC 658
Cdd:pfam16413 241 KDT-VVQVANLPDLYKVFERC 260
mutl TIGR00585
DNA mismatch repair protein MutL; All proteins in this family for which the functions are ...
 4-217 1.87e-80

DNA mismatch repair protein MutL; All proteins in this family for which the functions are known are involved in the process of generalized mismatch repair. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 273155 [Multi-domain]  Cd Length: 312  Bit Score: 257.57  E-value: 1.87e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010   4 EALASISHVAHVTITTKT-ADGKCAYRASYsDGKLKAPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVV 82
Cdd:TIGR00585  97 EALASISSVSRLTITTKTsAADGLAYQALL-EGGMIESIKPAPRPVGTTVEVRDLFYNLPVRRKFLKSPKKEFRKILDVL 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010  83 GRYSVHNAGISFSVKKQGETVADVRTLPNASTVDN-IRSIFGNAVSRELIEIGcEDKTLAFKMNGYISNANYSVKKCI-- 159
Cdd:TIGR00585 176 QRYALIHPDISFSLTHDGKKVLQLSTKPNQSTKENrIRSVFGTAVLRKLIPLD-EWEDLDLQLEGFISQPNVTRSRRSgw 254

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1233055010 160 FLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVH 217
Cdd:TIGR00585 255 QFLFINGRPVELKLLLKAIREVYHEYLPKGQYPVFVLNLEIDPELVDVNVHPDKKEVR 312
MutL_Trans_MLH1 cd03483
MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in ...
 113-237 5.48e-75

MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from ATP-binding site to the DNA breakage/reunion regions of the enzymes. MLH1 forms heterodimers with PMS2, PMS1 and MLH3. These three complexes have distinct functions in meiosis. hMLH1-hPMS2 also participates in the repair of all DNA mismatch repair (MMR) substrates. Roles for hMLH1-hPMS1 or hMLH1-hMLH3 in MMR have not been established. Cells lacking hMLH1 have a strong mutator phenotype and display microsatellite instability (MSI). Mutation in hMLH1 causes predisposition to HNPCC, Muir-Torre syndrome and Turcot syndrome (HNPCC variant). Mutation in hMLH1 accounts for a large fraction of HNPCC families.


Pssm-ID: 239565 [Multi-domain]  Cd Length: 127  Bit Score: 236.36  E-value: 5.48e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 113 STVDNIRSIFGNAVSRELIEIGCEDKT--LAFKMNGYISNANYSVKKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNT 190
Cdd:cd03483     1 STKDNIRSVYGAAVANELIEVEISDDDddLGFKVKGLISNANYSKKKIIFILFINNRLVECSALRRAIENVYANYLPKGA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1233055010 191 HPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKLL 237
Cdd:cd03483    81 HPFVYLSLEIPPENVDVNVHPTKREVHFLNEEEIIERIQKLVEDKLS 127
MutL COG0323
DNA mismatch repair ATPase MutL [Replication, recombination and repair];
4-239 2.12e-63

DNA mismatch repair ATPase MutL [Replication, recombination and repair];


Pssm-ID: 440092 [Multi-domain]  Cd Length: 515  Bit Score: 218.76  E-value: 2.12e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010   4 EALASISHVAHVTITTKTADGKCAYRASYSDGKLKaPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVVG 83
Cdd:COG0323    98 EALASIASVSRLTLTTRTAGAELGTRIEVEGGKVV-EVEPAAAPKGTTVEVRDLFFNTPARRKFLKSDATELAHITDVVR 176

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010  84 RYSVHNAGISFSVKKQGETVadVRTLPNASTVDNIRSIFGNAVSRELIEIgcEDKTLAFKMNGYISNANY--SVKKCIFL 161
Cdd:COG0323   177 RLALAHPDIAFTLIHNGREV--FQLPGAGDLLQRIAAIYGREFAENLLPV--EAEREGLRLSGYIGKPEFsrSNRDYQYF 252

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1233055010 162 lFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKLLGS 239
Cdd:COG0323   253 -FVNGRPVRDKLLSHAVREAYRDLLPKGRYPVAVLFLELDPELVDVNVHPTKTEVRFRDEREVYDLVRSAVREALAQA 329
mutL PRK00095
DNA mismatch repair endonuclease MutL;
4-329 2.12e-57

DNA mismatch repair endonuclease MutL;


Pssm-ID: 234630 [Multi-domain]  Cd Length: 617  Bit Score: 204.68  E-value: 2.12e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010   4 EALASISHVAHVTITTKTADGKCAYRASYSDGKLKaPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVVG 83
Cdd:PRK00095   97 EALPSIASVSRLTLTSRTADAAEGWQIVYEGGEIV-EVKPAAHPVGTTIEVRDLFFNTPARRKFLKSEKTELGHIDDVVN 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010  84 RYSVHNAGISFSVKKQGETVadVRTLPNASTVDNIRSIFGNAVSRELIEIGCEDktLAFKMNGYI-------SNANYsvk 156
Cdd:PRK00095  176 RLALAHPDVAFTLTHNGKLV--LQTRGAGQLLQRLAAILGREFAENALPIDAEH--GDLRLSGYVglptlsrANRDY--- 248

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 157 kcIFLlFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKL 236
Cdd:PRK00095  249 --QYL-FVNGRYVRDKLLNHAIRQAYHDLLPRGRYPAFVLFLELDPHQVDVNVHPAKHEVRFRDERLVHDLIVQAIQEAL 325

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 237 LGSN----------------SSRMYFTQTLLPGLAGPSGEMVKSTTSLTSSSTSGSSDKVYAHQMVRTDSREQKLDAFLQ 300
Cdd:PRK00095  326 AQSGlipaaaganqvlepaePEPLPLQQTPLYASGSSPPASSPSSAPPEQSEESQEESSAEKNPLQPNASQSEAAAAASA 405

                         330       340       350
                  ....*....|....*....|....*....|.
gi 1233055010 301 PLSK--PLSSQPQAIVTEDKTDISSGRARQQ 329
Cdd:PRK00095  406 EAAAaaPAAAPEPAEAAEEADSFPLGYALGQ 436
MutL_Trans cd00782
MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the ...
 116-236 5.87e-45

MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the C-terminal domain of DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from ATP-binding site to the DNA breakage/reunion regions of the enzymes. Included in this group are proteins similar to human MLH1, hPMS2, hPMS1, hMLH3 and E. coli MutL, MLH1 forms heterodimers with PMS2, PMS1 and MLH3. These three complexes have distinct functions in meiosis. hMLH1-hPMS2 also participates in the repair of all DNA mismatch repair (MMR) substrates. Roles for hMLH1-hPMS1 or hMLH1-hMLH3 in MMR have not been established. Cells lacking either hMLH1 or hPMS2 have a strong mutator phenotype and display microsatellite instability (MSI). Mutation in hMLH1 causes predisposition to HNPCC, Muir-Torre syndrome and Turcot syndrome (HNPCC variant). Mutation in hPMS2 causes predisposition to HPNCC and Turcot syndrome. Mutation in hMLH1 accounts for a large fraction of HNPCC families. There is no convincing evidence to support hPMS1 having a role in HNPCC predisposition. It has been suggested that hMLH3 may be a low risk gene for colorectal cancer; however there is little evidence to support it having a role in classical HNPCC. It has been suggested that during initiation of DNA mismatch repair in E. coli, the mismatch recognition protein MutS recruits MutL in the presence of ATP. The MutS(ATP)-MutL ternary complex formed, then recruits the latent endonuclease MutH.


Pssm-ID: 238405 [Multi-domain]  Cd Length: 122  Bit Score: 156.16  E-value: 5.87e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 116 DNIRSIFGNAVSRELIEIGCEDKTlaFKMNGYISNANYSV-KKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFL 194
Cdd:cd00782     3 DRIAQVYGKEVAKNLIEVELESGD--FRISGYISKPDFGRsSKDRQFLFVNGRPVRDKLLSKAINEAYRSYLPKGRYPVF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1233055010 195 YLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKL 236
Cdd:cd00782    81 VLNLELPPELVDVNVHPTKREVRFSDEEEVLELIREALRSAL 122
DNA_mis_repair pfam01119
DNA mismatch repair protein, C-terminal domain; This family represents the C-terminal domain ...
 119-236 4.16e-42

DNA mismatch repair protein, C-terminal domain; This family represents the C-terminal domain of the mutL/hexB/PMS1 family. This domain has a ribosomal S5 domain 2-like fold.


Pssm-ID: 426060 [Multi-domain]  Cd Length: 117  Bit Score: 148.03  E-value: 4.16e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 119 RSIFGNAVSRELIEIGCEDKTlaFKMNGYISNANYS-VKKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLS 197
Cdd:pfam01119   1 AAIYGKEFAENLLPIEKEDDG--LRLSGYISKPTLSrSNRDYQYLFVNGRPVRDKLLSHAIREAYRDLLPKGRYPVAVLF 78

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1233055010 198 LEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKL 236
Cdd:pfam01119  79 LEIDPELVDVNVHPTKREVRFRDEREVYDFIKEALREAL 117
HATPase_MutL-MLH-PMS-like cd16926
Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, ...
 4-103 1.25e-41

Histidine kinase-like ATPase domain of DNA mismatch repair proteins Escherichia coli MutL, human MutL homologs (MLH/ PMS), and related domains; This family includes the histidine kinase-like ATPase (HATPase) domains of Escherichia coli MutL, human MLH1 (mutL homolog 1), human PMS1 (PMS1 homolog 1, mismatch repair system component), human MLH3 (mutL homolog 3), and human PMS2 (PMS1 homolog 2, mismatch repair system component). MutL homologs (MLH/PMS) participate in MMR (DNA mismatch repair), and in addition have role(s) in DNA damage signaling and suppression of homologous recombination (recombination between partially homologous parental DNAs). The primary role of MutL in MMR is to mediate protein-protein interactions during mismatch recognition and strand removal; a ternary complex is formed between MutS, MutL, and the mismatched DNA, which activates the MutH endonuclease.


Pssm-ID: 340403 [Multi-domain]  Cd Length: 188  Bit Score: 149.51  E-value: 1.25e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010   4 EALASISHVAHVTITTKTADGKCAYRASYSDGKLKAPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVVG 83
Cdd:cd16926    88 EALASIASVSRLTITTRTADDDVGTRLVVDGGGIIEEVKPAAAPVGTTVTVRDLFYNTPARRKFLKSPKTELSKILDLVQ 167

                          90       100
                  ....*....|....*....|
gi 1233055010  84 RYSVHNAGISFSVKKQGETV 103
Cdd:cd16926   168 RLALAHPDVSFSLTHDGKLV 187
TopoII_MutL_Trans cd00329
MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the ...
 116-217 6.91e-23

MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the C-terminal domain of type II DNA topoisomerases (Topo II) and DNA mismatch repair (MutL/MLH1/PMS2) proteins. This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from ATP-binding site to the DNA breakage/reunion regions of the enzymes. The GyrB dimerizes in response to ATP binding, and is homologous to the N-terminal half of eukaryotic Topo II and the ATPase fragment of MutL. Type II DNA topoisomerases catalyze the ATP-dependent transport of one DNA duplex through another, in the process generating transient double strand breaks via covalent attachments to both DNA strands at the 5' positions. Included in this group are proteins similar to human MLH1 and PMS2. MLH1 forms a heterodimer with PMS2 which functions in meiosis and in DNA mismatch repair (MMR). Cells lacking either hMLH1 or hPMS2 have a strong mutator phenotype and display microsatellite instability (MSI). Mutation in hMLH1 accounts for a large fraction of Lynch syndrome (HNPCC) families.


Pssm-ID: 238202 [Multi-domain]  Cd Length: 107  Bit Score: 93.86  E-value: 6.91e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 116 DNIRSIFGNAVSRELIEIGCEDKTlaFKMNGYISNANYSV-KKCIFLLFINHRLV-ESTSLRKAIETVYAAYL---PKNT 190
Cdd:cd00329     3 DRLAEILGDKVADKLIYVEGESDG--FRVEGAISYPDSGRsSKDRQFSFVNGRPVrEGGTHVKAVREAYTRALngdDVRR 80

                          90       100
                  ....*....|....*....|....*..
gi 1233055010 191 HPFLYLSLEISPQNVDVNVHPTKHEVH 217
Cdd:cd00329    81 YPVAVLSLKIPPSLVDVNVHPTKEEVR 107
MutL_Trans_MutL cd03482
MutL_Trans_MutL: transducer domain, having a ribosomal S5 domain 2-like fold, found in ...
 118-236 9.10e-15

MutL_Trans_MutL: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to Escherichia coli MutL. EcMutL belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from the ATP-binding site to the DNA breakage/reunion regions of the enzymes. It has been suggested that during initiation of DNA mismatch repair in E. coli, the mismatch recognition protein MutS recruits MutL in the presence of ATP. The MutS(ATP)-MutL ternary complex formed, then recruits the latent endonuclease MutH. Prokaryotic MutS and MutL are homodimers.


Pssm-ID: 239564 [Multi-domain]  Cd Length: 123  Bit Score: 71.08  E-value: 9.10e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 118 IRSIFGNAVSRELIEIGCEDKTLafKMNGYISNANYS-VKKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYL 196
Cdd:cd03482     5 LADILGEDFAEQALAIDEEAGGL--RLSGWIALPTFArSQADIQYFYVNGRMVRDKLISHAVRQAYSDVLHGGRHPAYVL 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1233055010 197 SLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKL 236
Cdd:cd03482    83 YLELDPAQVDVNVHPAKHEVRFRDSRLVHDFIYHAVKKAL 122
MutL_Trans_hPMS_2_like cd03484
MutL_Trans_hPMS2_like: transducer domain, having a ribosomal S5 domain 2-like fold, found in ...
 116-234 5.82e-13

MutL_Trans_hPMS2_like: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to human PSM2 (hPSM2). hPSM2 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from ATP-binding site to the DNA breakage/reunion regions of the enzymes. Included in this group are proteins similar to yeast PMS1. The yeast MLH1-PMS1 and the human MLH1-PMS2 heterodimers play a role in meiosis. hMLH1-hPMS2 also participates in the repair of all DNA mismatch repair (MMR) substrates. Cells lacking hPMS2 have a strong mutator phenotype and display microsatellite instability (MSI). Mutation in hPMS2 causes predisposition to HPNCC and Turcot syndrome.


Pssm-ID: 239566 [Multi-domain]  Cd Length: 142  Bit Score: 66.52  E-value: 5.82e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 116 DNIRSIFGNAVSRELIEI---------------GCEDKTLAFKMNGYISnanysvkKCIF----------LLFINHRLVE 170
Cdd:cd03484     4 DNIINVFGGKVIKGLIPInleldvnptkeeldsDEDLADSEVKITGYIS-------KPSHgcgrsssdrqFFYINGRPVD 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1233055010 171 STSLRKAIETVYAAYlPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIES 234
Cdd:cd03484    77 LKKVAKLINEVYKSF-NSRQYPFFILNISLPTSLYDVNVTPDKRTVLLHDEDRLIDTLKTSLSE 139
MutL_Trans_hPMS_1_like cd03485
MutL_Trans_hPMS1_like: transducer domain, having a ribosomal S5 domain 2-like fold, found in ...
 120-234 6.97e-10

MutL_Trans_hPMS1_like: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to human PSM1 (hPSM1) and yeast MLH2. hPSM1 and yMLH2 are members of the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from ATP-binding site to the DNA breakage/reunion regions of the enzymes. PMS1 forms a heterodimer with MLH1. The MLH1-PMS1 complex functions in meiosis. Loss of yMLH2 results in a small but significant decrease in spore viability and a significant increase in gene conversion frequencies. A role for hMLH1-hPMS1 in DNA mismatch repair has not been established. Mutation in hMLH1 accounts for a large fraction of Lynch syndrome (HNPCC) families, however there is no convincing evidence to support hPMS1 having a role in HNPCC predisposition.


Pssm-ID: 239567 [Multi-domain]  Cd Length: 132  Bit Score: 57.28  E-value: 6.97e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 120 SIFGNAVSRELIEIGCEDKTLAFKMNGYI--SNANYSVKKCIF-LLFINHRLVESTS-LRKAIETVYAAYLPKNT---HP 192
Cdd:cd03485     8 RVLGTAVAANMVPVQSTDEDPQISLEGFLpkPGSDVSKTKSDGkFISVNSRPVSLGKdIGKLLRQYYSSAYRKSSlrrYP 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1233055010 193 FLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIES 234
Cdd:cd03485    88 VFFLNILCPPGLVDVNIEPDKDDVLLQNKEAVLQAVENLLES 129
MutL_Trans_MLH3 cd03486
MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in ...
 119-236 4.17e-03

MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to be important in nucleotide hydrolysis and the transduction of structural signals from ATP-binding site to the DNA breakage/reunion regions of the enzymes. MLH1 forms heterodimers with MLH3. The MLH1-MLH3 complex plays a role in meiosis. A role for hMLH1-hMLH3 in DNA mismatch repair (MMR) has not been established. It has been suggested that hMLH3 may be a low risk gene for colorectal cancer; however there is little evidence to support it having a role in classical HNPCC.


Pssm-ID: 239568 [Multi-domain]  Cd Length: 141  Bit Score: 38.07  E-value: 4.17e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1233055010 119 RSIFGNAVSRELIEIGCEDKTlaFKMNGYISNaNYSVKKCIFLLFINHRLVESTSLRKAIETVY----AAYLPKNT---- 190
Cdd:cd03486     7 KQIYGLVLAQKLKEVSAKFQE--YEVSGYISS-EGHYSKSFQFIYVNGRLYLKTRFHKLINKLFrktsAVAKNKSSpqsk 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1233055010 191 -----------HPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKL 236
Cdd:cd03486    84 ssrrgkrsqesYPVFVLNITCPASEYDLSQEPSKTIIEFKDWKTLLPLILEVVKSFL 140
 
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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