1B63,1EA6


Conserved Protein Domain Family
MutL_Trans
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cd00782: MutL_Trans 
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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.
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Statistics
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PSSM-Id: 238405
Aligned: 165 rows
Threshold Bit Score: 59.0921
Created: 6-Mar-2002
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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ATP binding
Conserved site include 1 residue -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:1B63_A, Escherichia coli MutL bound with Adpnp ((non-hydrolyzable ATP analog), contacts at 3.5A
  • Comment:conserved Lys residue from the transducer domain interacts with the gamma-phosphate of bound nucleotide.
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1                                                                                      
1B63_A     210 KERRLGAICGtaf-leqALAIEwqh---------gdlTLRGWVAdpnhttpaLAEIQYCYVNGRMMr-dRLINHAIRQAC 278  Escherichia coli
AAH73356   137 VRSRFCQIYGlpr-sqkLCEIQhkv---------kefDMWGYIScea---hyNKRMQYLYVNKRLVl-kTKLHQLIDFLL 202  African clawed frog
XP_638890  250 FLSYFKHFYGqem-mnkLEYVTsenynnttnnnsssyYLSGYLSsphkkghpNKSFQYIYLNNRIVl-nTKLHRHVNQLY 327  Dictyostelium di...
AAX59030   207 VCSRFCQIYGlgk-sqkLREISfky---------kefELSGYISsea---hyNKNMQFLFVNKRLVl-rTKLHKLIDFLL 272  human
XP_780519   83 IVQTFGYLFGkdv-adcLKEVNhir---------tifNVSGFIGsts---frNKSLQFVYVNGRLVl-kTKIHKLINELL 148  purple urchin
XP_421275  286 VYSRFCQIYGlgr-sqkLREIKhks---------ggfEISGYISseg---hyNKNMQFLYVNRRLVl-kTRLHKLIDFLL 351  chicken
EAL21089   219 ALDVFKTLYGgal-vqsVQKIKvta---------gkrKVDGFISisg---dvSKAHQHLYINNYPId-rGDVHTAIAKKF 284  Cryptococcus neo...
CAG88001   242 YATIFKSIYGhsl-lseYETVRanf---------qdyKLDGIIGlfp---sqSKAFQYIFVNQRPLlisNEDSKYLNKIF 308  Debaryomyces han...
CAG62407   241 IHNAFIRVYGhvvpdpsIKIVKlsf---------reyNITGLISncq---vrSKSFQFVFVNGRRYs-nSEFLGKINRIF 307  Candida glabrata...
NP_015161  234 MSQVLRNVFGaiippdmLKKVSlkf---------neyQIEGIISkmp---vgLKDLQFIYINGRRYa-dSAFQGYVDSLF 300  baker's yeast

Feature 1                                                                     #                
1B63_A     279 Edklg--------------------------------adqqPAFVLYLEIDPhqVDVNV-HPAKHEVRFhqSRLVHDFIY 325  Escherichia coli
AAH73356   203 Rkessickpkninvgk-----------ssspgrsrscqelhGIFVINIYCHYseYDVCF-EPAKTLIEFkdWDTVLHCVE 270  African clawed frog
XP_638890  328 Qkyrlfnatrkanan-------------vskiakkevidsnPIFILFLRCSQleYERSYePSSKTFLEFndWKKPLAEIQ 394  Dictyostelium di...
AAX59030   273 Rkesiickpkngptsr----------qmnsslrhrstpelyGIYVINVQCQFceYDVCM-EPAKTLIEFqnWDTLLFCIQ 341  human
XP_780519  149 SnslvtkskgknqdtalgytmksnaasstcqpspggnqveyGIFVLNITCPRseYDITL-DPSKTLIEFrdWEGAVTCVH 227  purple urchin
XP_421275  352 Rkesvickaksvpaskq---------gssspgrlrcgpelyGIFVLNVTCAYsdYDVSL-EPTKTLIEFqnWDVLLACVE 421  chicken
EAL21089   285 Asskfanlasagqhdede-------dyhpsgrrsprrleryPVYVLNVTLSAgeLDVSY-EPQKGVLGYkdIESLKTMLL 356  Cryptococcus neo...
CAG88001   309 Vtanfggmltstasnisls----pskvspnkqytsksfsrfPVFIINIQCPIiiEDLFQ-DPSKSIYYSnhMKLILNMLR 383  Debaryomyces han...
CAG62407   308 Dqstfatnavekd-----------------trlgkrsarsyPLFVIKIDGPAhvQDLIQ-STSKDIIHLsdGKLINILIL 369  Candida glabrata...
NP_015161  301 Qaqdfgekgmsll----------------ktksvgkpyrshPVFILDVRCPQtiDDLLQ-DPAKKIVKPshIRTIEPLIV 363  baker's yeast

Feature 1             
1B63_A     326 QGVLSVL 332  Escherichia coli
AAH73356   271 EGTRAFL 277  African clawed frog
XP_638890  395 NVLTKFL 401  Dictyostelium discoideum AX4
AAX59030   342 EGVKMFL 348  human
XP_780519  228 ELVTSFL 234  purple urchin
XP_421275  422 EGVKMFL 428  chicken
EAL21089   357 AVVDEFL 363  Cryptococcus neoformans var. neoformans B-3501A
CAG88001   384 NVFSSFL 390  Debaryomyces hansenii CBS767
CAG62407   370 KVIYSFL 376  Candida glabrata CBS138
NP_015161  364 KTIRSFL 370  baker's yeast

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