mutL:Gene Product(s): Difference between revisions

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|{{Sub}}[[#Localization |Localization]]
|{{Sub}}[[#Localization |Localization]]
|{{Sub}}[[#Sequence|Sequence]]
|{{Sub}}[[#Sequence|Sequence]]
|{{Sub}}[[#Domains/Motifs/Modification Sites|Domains]]
|{{Sub}}[[#Structure|Structure]]
|{{Sub}}[[#Structure|Structure]]
|{{Sub}}[[#Gene Product Resources|Resources]]
|{{Sub}}[[#Gene Product Resources|Resources]]
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{|{{Prettytable}}
{|  id="T46ab229740671"  class=" tableEdit Product_nomenclature_table" 
 
|-
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!{{table heading style}} |Standard name
!align=left {{table heading style}} |Standard name
|
||
MutL product
MutL
|-
|-
!{{table heading style}} |Synonyms
!align=left {{table heading style}} |Synonyms
|
||
methyl-directed mismatch repair protein product<ref name='LIB:Riley_2006'/>, B4170 product<ref name='LIB:EcoCyc10.6'/><ref name='LIB:Riley_2006'/>, MutL product<ref name='LIB:EcoCyc10.6'/><ref name='LIB:Riley_2006'/>  
''methyl-directed mismatch repair protein<ref name='LIB:Riley_2006'/>, B4170<ref name='LIB:EcoCyc10.6'/><ref name='LIB:Riley_2006'/>, MutL<ref name='LIB:EcoCyc10.6'/><ref name='LIB:Riley_2006'/> , ECK4166, JW4128, b4170''
|-
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!{{table heading style}} |Product description
!align=left {{table heading style}} |Product description
|
||
MutL<ref name='LIB:EcoCyc10.6'/><ref name='LIB:EcoCyc11.1'/>;  
MutL<ref name='LIB:EcoCyc10.6'/><ref name='LIB:EcoCyc11.1'/>;  


Component of ; [[:Category:Complex:MutHLS complex, methyl-directed mismatch repair|MutHLS complex, methyl-directed mismatch repair]]<ref name='LIB:EcoCyc10.6'/><ref name='LIB:EcoCyc11.1'/>
Component of [[:Category:Complex:MutHLS complex, methyl-directed mismatch repair|MutHLS complex, methyl-directed mismatch repair]]<ref name='LIB:EcoCyc10.6'/><ref name='LIB:EcoCyc11.1'/>


Methyl-directed mismatch repair; matchmaker protein; weak DNA-stimulated ATPase<ref name='LIB:EcoGene'/>
|-
|-
!{{table heading style}} |EC number (for enzymes)
!align=left {{table heading style}} |EC number (for enzymes)
|
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<protect><!--Nomenclature_notes--></protect>
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===Notes===
===Notes===
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<protect>
<protect>
<big>'''Gene Ontology'''</big>
<big>'''Gene Ontology'''</big><br /><!--box uid=421aa90e079fa326b6494f812ad13e79.29057.D46ab2298c363d-->
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{|class = 'sortable' border="2" cellpadding="4" cellspacing="0" style="margin: 1em 1em 1em 0; border: 1px #aaa solid; border-collapse: collapse;" {{Prettytable}}
{| border="2" cellpadding="4" cellspacing="0" style="margin: 1em 1em 1em 0; border: 1px #aaa solid; border-collapse: collapse;" id="D46ab2298c363d"  class=" tableEdit GO_table_product dataTable" 
|- {{table_heading_style}}
|- {{table_heading_style}}
!|Qualifier!!GO ID!!GO term name!!Reference(s)!!Evidence Code!!with/from!!Aspect!!Notes!!Status
!|Qualifier!!GO ID!!GO term name!!Reference!!Evidence Code!!with/from!!Aspect!!Notes!!Status
|-
|
 
|
GO:0006298
|
mismatch repair
|
PMID:6987663
|
IMP: Inferred from Mutant Phenotype
|
 
|
P
|
 
|
complete
|-
|
 
|
GO:0005524
|
ATP binding
|
PMID:9827806
|
IDA: Inferred from Direct Assay
|
 
|
F
|
 
|
complete
|-
|
 
|
GO:0006298
|
mismatch repair
|
PMID:2665076
|
IDA: Inferred from Direct Assay
|
 
|
P
|
 
|
complete
|-
|
 
|
GO:0032300
|
mismatch repair complex
|
PMID:6987663
|
IGI: Inferred from Genetic Interaction
|
UniProtKB:P06722|UniProtKB:P23909
|
C
|
With MutH (P06722) and MutS (P23909).
|
complete
|-  
|-  
|
|


|
|
[[Category:GO:0000166_!_nucleotide_binding]][http://gowiki.tamu.edu/wiki/index.php/Category:GO:0000166_!_nucleotide_binding GO:0000166]
GO:0005515
|
|
nucleotide_binding
protein binding
|
|
[http://www.geneontology.org/cgi-bin/references.cgi/#GO_REF:0000004 GO_REF:0000004]<br />
GOA:interpro<br />GO_REF:0000002
|
|
IEA: Inferred from Electronic Annotation
IEA: Inferred from Electronic Annotation
|
|
SP_KW:KW-0547
InterPro:IPR020667
|
|
F
F
|
|
Seeded from EcoCyc 12.5 <ref name = 'LIB:EcoCyc12.5'/>
Seeded from [[EcoCyc]] (v14.0)
|
|
complete
|-  
|-  
|
|
 
|
|
[[Category:GO:0006281_!_DNA_repair]][http://gowiki.tamu.edu/wiki/index.php/Category:GO:0006281_!_DNA_repair GO:0006281]
GO:0016887
|
|
DNA repair
ATPase activity
|
|
PMID:9827806
|
|
IDA: Inferred from Direct Assay
|
|
 
|
|
P
F
|
|
Seeded from EcoCyc 11.1<ref name='LIB:EcoCyc11.1'/>.
 
|
|
required fields missing 
complete
|-  
|-  
|
|
 
|
|
[[Category:GO:0005737_!_cytoplasm]][http://gowiki.tamu.edu/wiki/index.php/Category:GO:0005737_!_cytoplasm GO:0005737]
GO:0005524
|
|
cytoplasm
ATP binding
|
|
GOA:interpro<br />GO_REF:0000002
|
|
IEA: Inferred from Electronic Annotation
|
|
InterPro:IPR002099
|
|
C
F
|
|
Seeded from EcoCyc 11.1<ref name='LIB:EcoCyc11.1'/>.  
Seeded from [[EcoCyc]] (v14.0)
|
|
required fields missing 
complete
|-  
|-  
|
|
 
|
|
[[Category:GO:0006298_!_mismatch_repair]][http://gowiki.tamu.edu/wiki/index.php/Category:GO:0006298_!_mismatch_repair GO:0006298]
GO:0016887
|
|
mismatch repair
ATPase activity
|
|
[[PMID:6987663]]<ref name=PMID:6987663/>
PMID:9827806
|
|
IMP: Inferred from Mutant Phenotype
IMP: Inferred from Mutant Phenotype
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|
|
P
F
|
|


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|-  
|-  
|
|
 
|
|
[[Category:GO:0005524_!_ATP_binding]][http://gowiki.tamu.edu/wiki/index.php/Category:GO:0005524_!_ATP_binding GO:0005524]
GO:0005524
|
|
ATP binding
ATP binding
|
|
[[PMID:9827806]]<ref name=PMID:9827806/>  
GOA:interpro<br />GO_REF:0000002
|
|
IDA: Inferred from Direct Assay
IEA: Inferred from Electronic Annotation
|
InterPro:IPR003594
|
F
|
Seeded from [[EcoCyc]] (v14.0)
|
complete
|-
|
|


|
GO:0005524
|
ATP binding
|
GOA:interpro<br />GO_REF:0000002
|
IEA: Inferred from Electronic Annotation
|
InterPro:IPR013507
|
|
F
F
|
Seeded from [[EcoCyc]] (v14.0)
|
complete
|-
|
|


|
GO:0005524
|
ATP binding
|
GOA:spkw<br />SP_KW:GO_REF:0000004
|
IEA: Inferred from Electronic Annotation
|
SP_KW:KW-0067
|
F
|
Seeded from [[EcoCyc]] (v14.0)
|
|
complete  
complete  
|-  
|-  
|
|
 
|
GO:0006298
|
mismatch repair
|
GOA:hamap<br />GO_REF:0000020
|
IEA: Inferred from Electronic Annotation
|
HAMAP:MF_00149
|
P
|
Seeded from [[EcoCyc]] (v14.0)
|
complete
|-
|
 
|
GO:0006298
|
mismatch repair
|
GOA:interpro<br />GO_REF:0000002
|
IEA: Inferred from Electronic Annotation
|
InterPro:IPR002099
|
P
|
Seeded from [[EcoCyc]] (v14.0)
|
complete
|-
|
 
|
|
[[Category:GO:0006298_!_mismatch_repair]][http://gowiki.tamu.edu/wiki/index.php/Category:GO:0006298_!_mismatch_repair GO:0006298]
GO:0006298
|
|
mismatch repair
mismatch repair
|
|
[[PMID:2665076]]<ref name=PMID:2665076/>
GOA:interpro<br />GO_REF:0000002
|
|
IDA: Inferred from Direct Assay
IEA: Inferred from Electronic Annotation
|
InterPro:IPR013507
|
P
|
Seeded from [[EcoCyc]] (v14.0)
|
complete
|-
|
|


|
GO:0006298
|
mismatch repair
|
GOA:interpro<br />GO_REF:0000002
|
IEA: Inferred from Electronic Annotation
|
InterPro:IPR020667
|
|
P
P
|
Seeded from [[EcoCyc]] (v14.0)
|
complete
|-
|
|


|
GO:0030983
|
mismatched DNA binding
|
GOA:interpro<br />GO_REF:0000002
|
IEA: Inferred from Electronic Annotation
|
InterPro:IPR002099
|
F
|
Seeded from [[EcoCyc]] (v14.0)
|
|
complete  
complete  
Line 195: Line 388:


|
|
[[Category:GO:0032300_!_mismatch_repair_complex]][http://gowiki.tamu.edu/wiki/index.php/Category:GO:0032300_!_mismatch_repair_complex GO:0032300]
GO:0030983
|
mismatched DNA binding
|
GOA:interpro<br />GO_REF:0000002
|
|
mismatch repair complex
IEA: Inferred from Electronic Annotation
|
InterPro:IPR013507
|
F
|
Seeded from [[EcoCyc]] (v14.0)
|
complete
|-
|
 
|
GO:0005524
|
ATP binding
|
|
[[PMID:6987663]]<ref name=PMID:6987663/>
PMID:12606120
|
|
IGI: Inferred from Genetic Interaction
IDA: Inferred from Direct Assay
|
|
UniProtKB:P06722|UniProtKB:P23909
 
|
|
C
F
|
|
With MutH (P06722) and MutS (P23909).
 
|
|
complete  
complete  
|-  
|-  
|
|
 
|
|
[[Category:GO:0016887_!_ATPase_activity]][http://gowiki.tamu.edu/wiki/index.php/Category:GO:0016887_!_ATPase_activity GO:0016887]
GO:0003677
|
|
ATPase activity
DNA binding
|
|
[[PMID:9827806]]<ref name=PMID:9827806/>
PMID:12606120
|
|
IDA: Inferred from Direct Assay
IDA: Inferred from Direct Assay
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|-  
|-  
|
|
 
|
|
[[Category:GO:0016887_!_ATPase_activity]][http://gowiki.tamu.edu/wiki/index.php/Category:GO:0016887_!_ATPase_activity GO:0016887]
GO:0016887
|
|
ATPase activity
ATPase activity
|
|
[[PMID:9827806]]<ref name=PMID:9827806/>
PMID:9827806
|
|
IMP: Inferred from Mutant Phenotype
IDA: Inferred from Direct Assay
|
|


Line 252: Line 464:


|
|
[[Category:GO:0005515_!_protein_binding]][http://gowiki.tamu.edu/wiki/index.php/Category:GO:0005515_!_protein_binding GO:0005515]
GO:0005524
|
|
protein_binding
ATP binding
|
|
[[PMID:15690043]]<ref name=PMID:15690043/><br />
PMID:9827806
|
|
IPI: Inferred from Physical Interaction
IDA: Inferred from Direct Assay
|
|
UniProtKB:P0A6N1
 
|
|
F
F
|
|
Seeded from EcoCyc 12.5 <ref name = 'LIB:EcoCyc12.5'/>
 
|
complete
|-
|
 
|
|
GO:0000018
|
regulation of DNA recombination
|
PMID:2555716
|
IMP: Inferred from Mutant Phenotype
|
 
|
P
|
 
|
complete


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<span id="Interactions"></span><big>'''Interactions'''</big>
<span id="Interactions"></span><big>'''Interactions'''</big>
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!Partner Type!!Partner!!Notes
!|Partner Type!!Partner!!Notes!!References!!Evidence
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Protein
Protein
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Subunits of [[:Category:Complex:MutHLS complex, methyl-directed mismatch repair|MutHLS complex, methyl-directed mismatch repair]]  
Subunits of [[:Category:Complex:MutHLS complex, methyl-directed mismatch repair|MutHLS complex, methyl-directed mismatch repair]]  
|
|
Inferred from genetic interaction <ref name=PMID:6987663/>  
 
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PMID:6987663
|
Inferred from genetic interaction  
|-
|
Protein
|
tufA<br />
|
 
|
PMID:15690043
|
Experiment(s):EBI-880976<br />
|-
|
Protein
|
dnaK<br />
|
 
|
PMID:15690043
|
Experiment(s):EBI-887579<br />
|-
|
Protein
|
rpsA<br />
|
 
|
PMID:15690043
|
Experiment(s):EBI-887579<br />  
|-
|
Protein
|
rpsA
|
 
|
PMID:19402753
|
LCMS(ID Probability):99.6
|-
|
Protein
|
Vsr
|
 
|
PMID:19376855
|
|-
|
Protein
|
DnaN: beta sliding clamp of DNA Pol III
|
MutL only binds to the beta subunit in the presence of ss DNA.
|
PMID:16546997
|
native gel electrophoresis
|-
|
Protein
|
MutH
|
data suggest the ATPase fragment of MutL directly contacts MutH
|
PMID:9827806
|
Chemical crosslinking
|-
|
Protein
|
MutS
|
 
|
PMID:9250691
|
Visualized using EM
|-
|
Protein
|
UvrD
|
 
|
PMID:9880500
|
2-Hybrid Screen
|-
|
Protein
|
MutH
|
The C-terminal 218 amino acids of MutL were sufficient for the two-hybrid interaction with MutH
|
PMID:9880500
|
2 Hybrid Screen
|-
|
Protein
|
UvrD
|
Both the N- and C-termini of UvrD were required for interaction with MutL
|
PMID:9482750
|
2 Hybrid Screen
|-
|
Protein
|
[[recA:Gene_Product(s)|RecA]]
|
The N-terminal fragment of MutL (residues 1-349) was sufficient to bind RecA. 
 
MutL inhibits the ssDNA-dependent ATPase activity of RecA (Fig. 4)
|
PMID:22001225
|
Far-Western and pull-down assays.
 
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<!--Function_notes--></protect>
<!--Function_notes--></protect>
===Notes===
===Notes===
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!Compartment!!Description!!Evidence!!Notes
!|Compartment!!Description!!Evidence!!Reference/Source!!Notes
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{|{{Prettytable}}
{|   id="K46ab22a35502c"  class=" tableEdit Product_phys_prop_table" 
 
|-
!align=left {{table heading style}} |Name
||
 
|-
|-
!{{table heading style}} |Sequence
!align=left {{table heading style}} |Sequence
|
||
[http://biocyc.org/ECOLI/sequence-aa?object=EG11281-MONOMER at EcoCyc]  
[http://biocyc.org/ECOLI/sequence-aa?object=EG11281-MONOMER at EcoCyc]  
<pre>MPIQVLPPQL ANQIAAGEVV ERPASVVKEL VENSLDAGAT RIDIDIERGG AKLIRIRDNG
<pre>MPIQVLPPQL ANQIAAGEVV ERPASVVKEL VENSLDAGAT RIDIDIERGG AKLIRIRDNG
Line 350: Line 725:
QSVDLHPAIK ALKDE</pre>  
QSVDLHPAIK ALKDE</pre>  
|-
|-
!{{table heading style}} |Mol. Wt
!align=left {{table heading style}} |Length
|
||
67.92 kDa (calc) <ref name='LIB:EcoCyc10.6'/>
615
|-
|-
!{{table heading style}} |pI
!align=left {{table heading style}} |Mol. Wt
|
||
67.924 kDa
|-
|-
!{{table heading style}} |Extinction coefficient
!align=left {{table heading style}} |pI
|
||
54890 - 55765 (calc based on 11 Y, 7 W, and 7 C residues)  
6.8 (calculated)
|-
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!align=left {{table heading style}} |Extinction coefficient
||
54,890 - 55,765 (calc based on 11 Y, 7 W, and 7 C residues)
 
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<big>'''Domains/Motifs/Modification Sites'''</big>
 
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<span id="Domains/Motifs/Modification Sites"><big>'''Domains/Motifs/Modification Sites'''</big></span><table>
<tr align="left" valign="top">
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|- {{table heading style}}
|- {{table heading style}}
!Type!!Residues!!Description!!Notes
!|Type!!Residues!!Description!!Notes!!References
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Domain
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{{Product_domains_motifs_help}}
18..147
|
[http://pfam.janelia.org/family/PF02518 PF02518  Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase]
|


<span id="Structure"></span><big>'''Structure'''</big>
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!Structure Type!!Organism!!Accession!!Residues covered!!Notes
|-
|
|
X-RAY DIFFRACTION
PMID:19920124
|-  
|
Domain
|
212..331
|
|
Escherichia coli
[http://pfam.janelia.org/family/PF01119 PF01119 DNA mismatch repair protein, C-terminal domain]
   
|
|
[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1BKN 1BKN] CRYSTAL STRUCTURE OF AN N-TERMINAL 40KD FRAGMENT OF E. COLI DNA MISMATCH REPAIR PROTEIN MUTL
 
|
|
PMID:19920124
|-
|
|
 
Domain
|-
|
|
X-RAY DIFFRACTION
434..576
|
|
Escherichia coli
[http://pfam.janelia.org/family/PF08676 PF08676 MutL C terminal dimerisation domain]
   
|
|
[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1B63 1B63] MUTL COMPLEXED WITH ADPNP
 
|
|
PMID:19920124
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<td>
<!-- motifs column 2-->
   
   
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<motif_map/>
 
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</table>
 
<table><tr valign='top'><td>
<span id='Structure'></span><big>'''Structure'''</big><br />
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|-
!align=left {{table heading style}} |Structures
||
<beststructure>
gene=mutL
taxon=562,83333
</beststructure>
|-
!align=left {{table heading style}} |Models
||
View models at:
* [http://www.proteinmodelportal.org/query/uniprot/P23367 Protein Model Portal]
* [http://bioinf.cs.ucl.ac.uk/genome3d/read?uniprot_id=P23367 PSI-PRED (P23367)]
* [http://spock.genes.nig.ac.jp/~genome/cgi-bin/gkeytext.pl.cgi?A&QUERY1=P23367 Genomes TO Protein (P23367)] (GTOP)
 
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<!--Structure_notes--></protect>
</td><td></protect>
==== Structure figures ====
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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===Notes===
===Notes===


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!Resource type!!Source!!Notes/Reference
!|Resource type!!Source!!Notes/Reference
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|
Purified protein
|
MutL R266E<ref name='PMID:12606120'/>
|
*Behaves like &Delta;''mutL''
*Reduced DNA binding activity
*Is completely inactive in MMR and in blocking homologous recombination ''in vivo''
*Activates MutH ~50% better than wt MutL
*Basal level ATPase activity similar to wt MutL, which no longer responds to DNA stimulation
|-
|
Purified protein
|
MutL R95F<ref name='PMID:12606120'/>
|
*Mildly defective ATPase activity
*Defective MutH activation ''in vitro''
*Moderately elevated mutation and DNA recombination rates ''in vivo''
|-
|
Purified protein
|
MutL N302A<ref name='PMID:12606120'/>
|
* Mildly defective ATPase activity
* Defective MutH activation ''in vitro''
* Moderately elevated mutation and DNA recombination rates ''in vivo''
|-
|
Purified protein
|
MutL R261H<ref name='PMID:12606120'/>
|
*Reduced ATP binding
*Exhibit a 20-80% reduction in the ATP-dependent activation of MutH endonuclease activity
|-
|
Purified protein
|
MutL K307A<ref name='PMID:12606120'/>
|
*Reduced ATP binding
*Exhibit a 20-80% reduction in the ATP-dependent activation of MutH endonuclease activity
|-
|
Purified protein
|
MutL E29A<ref name='PMID:12606120'/>
|
*Binds ATP well, but hydrolyzes it poorly
*Activates MutH well, but fails to mediate the mismatch-dependent MutH activation by MutS in the MMR initiation assays 
|-
|
Purified protein
|
MutL R95F/N302A<ref name='PMID:12606120'/>
|
*Binds ATP well, but hydrolyzes it poorly
*Activates MutH well, but fails to mediate the mismatch-dependent MutH activation by MutS in the MMR initiation assays 
|-
|
Purified protein
|
MutL I90R<ref name='PMID:12606120'/>
|
*Behave like wt MutL ''in vitro'' and ''in vivo'' 
|-
|
Purified protein
|
MutL I90E<ref name='PMID:12606120'/>
|
*Behave like wt MutL ''in vitro'' and ''in vivo'' 
|-
|
Purified protein
|
MutL R237E<ref name='PMID:12606120'/>
|
*Behave like wt MutL ''in vitro'' and ''in vivo'' 
|-
|
Purified protein
|
MutL G238A<ref name='PMID:12606120'/>
|
*Appears to have no ''in vivo'' defect
*Insolubility issues prevented ''in vitro'' assays
|-
|
Purified protein
|
MutL K159E<ref name='PMID:12606120'/>
|
*Alters the residues around the DNA binding cleft
*~10-fold reduction in ATP hydrolysis
*Defective in DNA binding
*Fails to activate MMR and block homologous recombination
|-
|
Purified protein
|
MutL G238D<ref name='PMID:12606120'/>
|
*Confers a dominant mutator phenotype
*Insolubility issues prevented ''in vitro'' assays
|-
|
Purified protein
|
MutL R177E<ref name='PMID:12606120'/>
|
*Alters the residues around the DNA binding cleft
*Exhibits reduced catalytic efficiency
*Mediates the mismatch-dependent activation of MutH ''in vitro''
*Exhibits a mutator phenotype and increased homologous recombination ''in vivo''
|-
|
Purification protocol
|
Single-step purification of His6-MutL
|
PMID:8747662
 
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===Notes===
===Notes===
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|- {{table_heading_style}}
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!Database!!Accession!!Notes
!|Database!!Accession!!Notes
|-
|-
|
[http://www.ncbi.nlm.nih.gov/protein NCBI (Protein)] ([[NCBI (Protein)|EcoliWiki Page]])
|
[http://www.ncbi.nlm.nih.gov/protein/16131992 GI:16131992]
|
Escherichia coli str. K-12 substr. MG1655
|-
|
[http://www.ncbi.nlm.nih.gov/protein NCBI (Protein)] ([[NCBI (Protein)|EcoliWiki Page]])
|
[http://www.ncbi.nlm.nih.gov/protein/NP_418591.1 GeneID:948691]
|
Escherichia coli str. K-12 substr. MG1655
|-
|
[[ASAP]]
|
ASAP:ABE-0013655
|
''Escherichia coli'' str. K-12 substr. [[:Category:Strain:MG1655|MG1655]]
|-  
|
|
[http://ecocyc.org EcoCyc] ([[EcoCyc|EcoliWiki Page]])  
[http://www.pir.uniprot.org/ UniProt] ([[UniProt|EcoliWiki Page]])
|
|
[http://biocyc.org/ECOLI/NEW-IMAGE?type=NIL&object=EG11281-MONOMER EcoCyc:EG11281-MONOMER]
[http://www.uniprot.org/uniprot/P23367 UniProtKB/Swiss-Prot:P23367]
|
|
Escherichia coli str. K-12 substr. MG1655
|-
|-  
|
|
[http://uniprot.org/ UniProt] ([[UniProt|EcoliWiki Page]])
[[EcoCyc]]
|
|
[[uniprot:P23367|UniProt:P23367]] 
EcoCyc:EG11281
|
|
''Escherichia coli'' str. K-12 substr. [[:Category:Strain:MG1655|MG1655]]
|-
|-  
|
|
[http://pfam.sanger.ac.uk/ PFAM] ([[PFAM|EcoliWiki Page]])
[[EcoGene]]
|
|
[http://pfam.sanger.ac.uk/family?acc=PF02518 PFAM:PF02518] 
EcoGene:EG11281
|
|
''Escherichia coli'' str. K-12 substr. [[:Category:Strain:MG1655|MG1655]]
|-
|-  
|
|
[http://www.ncbi.nlm.nih.gov/RefSeq/ RefSeq] ([[RefSeq|EcoliWiki Page]])  
[http://www.ncbi.nlm.nih.gov/gene NCBI (Gene)] ([[NCBI (Gene)|EcoliWiki Page]])
|
|
[http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=NP_418591 RefSeq:NP_418591]
[http://www.ncbi.nlm.nih.gov/gene?term=948691 GeneID:948691]
|
|
Escherichia coli str. K-12 substr. MG1655
|-
|-  
|
|
[http://modbase.compbio.ucsf.edu ModBase] ([[ModBase|EcoliWiki Page]])
[[RegulonDB]]
|
|
[http://salilab.org/modbase/searchbyid?databaseID=P23367 ModBase:P23367] 
RegulonDB:ECK120001254
|
|
''Escherichia coli'' str. K-12 substr. [[:Category:Strain:MG1655|MG1655]]
|-
|-  
|
|
[http://www.rcsb.org/pdb PDB] ([[PDB|EcoliWiki Page]])
[[EchoBASE]]
|
|
[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1B63 PDB:1B63] 
EchoBASE:EB1258
|
|
''Escherichia coli'' str. K-12 substr. [[:Category:Strain:MG1655|MG1655]]
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===Notes===
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{{RefHelp}}
{{RefHelp}}
<references/>
<references />
__NOTOC__
__NOTOC__
</noinclude>
===Categories===
===Categories===
{{BacktoTop}}
{{BacktoTop}}
[[Category:Proteins]]
[[Category:Proteins]]
[[Category:GO:0006281_!_DNA repair]][[Category:GO:0005737_!_cytoplasm]][[Category:Complex:MutHLS complex, methyl-directed mismatch repair]][[Category:Products with structures in PDB]]
[[Category:RefGenome_Annotated_Gene]]

Latest revision as of 21:13, 17 February 2015

{{#css:Suppresslinks.css}}<css>h1 .editsection { display:none;} h2 .editsection { display:none;}</css>

Quickview   Gene   Gene Product(s)   Expression   Evolution   On One Page    
Nomenclature Function Interactions Localization Sequence Domains Structure Resources Accessions Links References Suggestions

Nomenclature

See Help:Product_nomenclature for help entering or editing information in this section of EcoliWiki.

Standard name

MutL

Synonyms

methyl-directed mismatch repair protein[1], B4170[2][1], MutL[2][1] , ECK4166, JW4128, b4170

Product description

MutL[2][3];

Component of MutHLS complex, methyl-directed mismatch repair[2][3]

Methyl-directed mismatch repair; matchmaker protein; weak DNA-stimulated ATPase[4]

EC number (for enzymes)


edit table


Notes

Function

[back to top]


Gene Ontology
See Help:Gene_ontology for help entering or editing GO terms and GO annotations in EcoliWiki.

Qualifier GO ID GO term name Reference Evidence Code with/from Aspect Notes Status
GO:0006298

mismatch repair

PMID:6987663[5]

IMP: Inferred from Mutant Phenotype

P

complete

GO:0005524

ATP binding

PMID:9827806[6]

IDA: Inferred from Direct Assay

F

complete

GO:0006298

mismatch repair

PMID:2665076[7]

IDA: Inferred from Direct Assay

P

complete

GO:0032300

mismatch repair complex

PMID:6987663[5]

IGI: Inferred from Genetic Interaction

UniProtKB:P06722|UniProtKB:P23909

C

With MutH (P06722) and MutS (P23909).

complete

GO:0005515

protein binding

GOA:interpro
GO_REF:0000002

IEA: Inferred from Electronic Annotation

InterPro:IPR020667

F

Seeded from EcoCyc (v14.0)

complete

GO:0016887

ATPase activity

PMID:9827806[6]

IDA: Inferred from Direct Assay

F

complete

GO:0005524

ATP binding

GOA:interpro
GO_REF:0000002

IEA: Inferred from Electronic Annotation

InterPro:IPR002099

F

Seeded from EcoCyc (v14.0)

complete

GO:0016887

ATPase activity

PMID:9827806[6]

IMP: Inferred from Mutant Phenotype

F

complete

GO:0005524

ATP binding

GOA:interpro
GO_REF:0000002

IEA: Inferred from Electronic Annotation

InterPro:IPR003594

F

Seeded from EcoCyc (v14.0)

complete

GO:0005524

ATP binding

GOA:interpro
GO_REF:0000002

IEA: Inferred from Electronic Annotation

InterPro:IPR013507

F

Seeded from EcoCyc (v14.0)

complete

GO:0005524

ATP binding

GOA:spkw
SP_KW:GO_REF:0000004

IEA: Inferred from Electronic Annotation

SP_KW:KW-0067

F

Seeded from EcoCyc (v14.0)

complete

GO:0006298

mismatch repair

GOA:hamap
GO_REF:0000020

IEA: Inferred from Electronic Annotation

HAMAP:MF_00149

P

Seeded from EcoCyc (v14.0)

complete

GO:0006298

mismatch repair

GOA:interpro
GO_REF:0000002

IEA: Inferred from Electronic Annotation

InterPro:IPR002099

P

Seeded from EcoCyc (v14.0)

complete

GO:0006298

mismatch repair

GOA:interpro
GO_REF:0000002

IEA: Inferred from Electronic Annotation

InterPro:IPR013507

P

Seeded from EcoCyc (v14.0)

complete

GO:0006298

mismatch repair

GOA:interpro
GO_REF:0000002

IEA: Inferred from Electronic Annotation

InterPro:IPR020667

P

Seeded from EcoCyc (v14.0)

complete

GO:0030983

mismatched DNA binding

GOA:interpro
GO_REF:0000002

IEA: Inferred from Electronic Annotation

InterPro:IPR002099

F

Seeded from EcoCyc (v14.0)

complete

GO:0030983

mismatched DNA binding

GOA:interpro
GO_REF:0000002

IEA: Inferred from Electronic Annotation

InterPro:IPR013507

F

Seeded from EcoCyc (v14.0)

complete

GO:0005524

ATP binding

PMID:12606120[8]

IDA: Inferred from Direct Assay

F

complete

GO:0003677

DNA binding

PMID:12606120[8]

IDA: Inferred from Direct Assay

F

complete

GO:0016887

ATPase activity

PMID:9827806[6]

IDA: Inferred from Direct Assay

F

complete

GO:0005524

ATP binding

PMID:9827806[6]

IDA: Inferred from Direct Assay

F

complete

GO:0000018

regulation of DNA recombination

PMID:2555716[9]

IMP: Inferred from Mutant Phenotype

P

complete

edit table

Interactions See Help:Product_interactions for help entering or editing information about gene product interactions in this section of EcoliWiki.

Partner Type Partner Notes References Evidence

Protein

Subunits of MutHLS complex, methyl-directed mismatch repair

PMID:6987663[5]

Inferred from genetic interaction

Protein

tufA

PMID:15690043[10]

Experiment(s):EBI-880976

Protein

dnaK

PMID:15690043[10]

Experiment(s):EBI-887579

Protein

rpsA

PMID:15690043[10]

Experiment(s):EBI-887579

Protein

rpsA

PMID:19402753[11]

LCMS(ID Probability):99.6

Protein

Vsr

PMID:19376855[12]

Protein

DnaN: beta sliding clamp of DNA Pol III

MutL only binds to the beta subunit in the presence of ss DNA.

PMID:16546997[13]

native gel electrophoresis

Protein

MutH

data suggest the ATPase fragment of MutL directly contacts MutH

PMID:9827806[6]

Chemical crosslinking

Protein

MutS

PMID:9250691[14]

Visualized using EM

Protein

UvrD

PMID:9880500[15]

2-Hybrid Screen

Protein

MutH

The C-terminal 218 amino acids of MutL were sufficient for the two-hybrid interaction with MutH

PMID:9880500[15]

2 Hybrid Screen

Protein

UvrD

Both the N- and C-termini of UvrD were required for interaction with MutL

PMID:9482750[16]

2 Hybrid Screen

Protein

RecA

The N-terminal fragment of MutL (residues 1-349) was sufficient to bind RecA.

MutL inhibits the ssDNA-dependent ATPase activity of RecA (Fig. 4)

PMID:22001225[17]

Far-Western and pull-down assays.

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Notes

Localization

See Help:Product_localization for how to add or edit information in this section of EcoliWiki.

Compartment Description Evidence Reference/Source Notes
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Notes

Structure and Physical Properties

[back to top]


Physical Properties See Help:Product_physical_properties for help entering or editing information about the physical properties of this gene product.

Name
Sequence

at EcoCyc 

MPIQVLPPQL ANQIAAGEVV ERPASVVKEL VENSLDAGAT RIDIDIERGG AKLIRIRDNG
CGIKKDELAL ALARHATSKI ASLDDLEAII SLGFRGEALA SISSVSRLTL TSRTAEQQEA
WQAYAEGRDM NVTVKPAAHP VGTTLEVLDL FYNTPARRKF LRTEKTEFNH IDEIIRRIAL
ARFDVTINLS HNGKIVRQYR AVPEGGQKER RLGAICGTAF LEQALAIEWQ HGDLTLRGWV
ADPNHTTPAL AEIQYCYVNG RMMRDRLINH AIRQACEDKL GADQQPAFVL YLEIDPHQVD
VNVHPAKHEV RFHQSRLVHD FIYQGVLSVL QQQLETPLPL DDEPQPAPRS IPENRVAAGR
NHFAEPAARE PVAPRYTPAP ASGSRPAAPW PNAQPGYQKQ QGEVYRQLLQ TPAPMQKLKA
PEPQEPALAA NSQSFGRVLT IVHSDCALLE RDGNISLLSL PVAERWLRQA QLTPGEAPVC
AQPLLIPLRL KVSAEEKSAL EKAQSALAEL GIDFQSDAQH VTIRAVPLPL RQQNLQILIP
ELIGYLAKQS VFEPGNIAQW IARNLMSEHA QWSMAQAITL LADVERLCPQ LVKTPPGGLL
QSVDLHPAIK ALKDE
Length

615

Mol. Wt

67.924 kDa

pI

6.8 (calculated)

Extinction coefficient

54,890 - 55,765 (calc based on 11 Y, 7 W, and 7 C residues)

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Domains/Motifs/Modification Sites

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Type Residues Description Notes References

Domain

18..147

PF02518 Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

PMID:19920124[18]

Domain

212..331

PF01119 DNA mismatch repair protein, C-terminal domain

PMID:19920124[18]

Domain

434..576

PF08676 MutL C terminal dimerisation domain

PMID:19920124[18]

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<motif_map/>

Structure
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Structures

<beststructure> gene=mutL taxon=562,83333 </beststructure>

Models

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Structure figures

Notes

Gene Product Resources

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Resource type Source Notes/Reference

Purified protein

MutL R266E[8]

  • Behaves like ΔmutL
  • Reduced DNA binding activity
  • Is completely inactive in MMR and in blocking homologous recombination in vivo
  • Activates MutH ~50% better than wt MutL
  • Basal level ATPase activity similar to wt MutL, which no longer responds to DNA stimulation

Purified protein

MutL R95F[8]

  • Mildly defective ATPase activity
  • Defective MutH activation in vitro
  • Moderately elevated mutation and DNA recombination rates in vivo

Purified protein

MutL N302A[8]

  • Mildly defective ATPase activity
  • Defective MutH activation in vitro
  • Moderately elevated mutation and DNA recombination rates in vivo

Purified protein

MutL R261H[8]

  • Reduced ATP binding
  • Exhibit a 20-80% reduction in the ATP-dependent activation of MutH endonuclease activity

Purified protein

MutL K307A[8]

  • Reduced ATP binding
  • Exhibit a 20-80% reduction in the ATP-dependent activation of MutH endonuclease activity

Purified protein

MutL E29A[8]

  • Binds ATP well, but hydrolyzes it poorly
  • Activates MutH well, but fails to mediate the mismatch-dependent MutH activation by MutS in the MMR initiation assays

Purified protein

MutL R95F/N302A[8]

  • Binds ATP well, but hydrolyzes it poorly
  • Activates MutH well, but fails to mediate the mismatch-dependent MutH activation by MutS in the MMR initiation assays

Purified protein

MutL I90R[8]

  • Behave like wt MutL in vitro and in vivo

Purified protein

MutL I90E[8]

  • Behave like wt MutL in vitro and in vivo

Purified protein

MutL R237E[8]

  • Behave like wt MutL in vitro and in vivo

Purified protein

MutL G238A[8]

  • Appears to have no in vivo defect
  • Insolubility issues prevented in vitro assays

Purified protein

MutL K159E[8]

  • Alters the residues around the DNA binding cleft
  • ~10-fold reduction in ATP hydrolysis
  • Defective in DNA binding
  • Fails to activate MMR and block homologous recombination

Purified protein

MutL G238D[8]

  • Confers a dominant mutator phenotype
  • Insolubility issues prevented in vitro assays

Purified protein

MutL R177E[8]

  • Alters the residues around the DNA binding cleft
  • Exhibits reduced catalytic efficiency
  • Mediates the mismatch-dependent activation of MutH in vitro
  • Exhibits a mutator phenotype and increased homologous recombination in vivo

Purification protocol

Single-step purification of His6-MutL

PMID:8747662[19]

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Notes

Accessions in Other Databases

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Database Accession Notes

NCBI (Protein) (EcoliWiki Page)

GI:16131992

Escherichia coli str. K-12 substr. MG1655

NCBI (Protein) (EcoliWiki Page)

GeneID:948691

Escherichia coli str. K-12 substr. MG1655

ASAP

ASAP:ABE-0013655

Escherichia coli str. K-12 substr. MG1655

UniProt (EcoliWiki Page)

UniProtKB/Swiss-Prot:P23367

Escherichia coli str. K-12 substr. MG1655

EcoCyc

EcoCyc:EG11281

Escherichia coli str. K-12 substr. MG1655

EcoGene

EcoGene:EG11281

Escherichia coli str. K-12 substr. MG1655

NCBI (Gene) (EcoliWiki Page)

GeneID:948691

Escherichia coli str. K-12 substr. MG1655

RegulonDB

RegulonDB:ECK120001254

Escherichia coli str. K-12 substr. MG1655

EchoBASE

EchoBASE:EB1258

Escherichia coli str. K-12 substr. MG1655

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Notes

Links

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References

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  1. ↑ 1.0 1.1 1.2 Riley, M. et al. (2006) Nucleic Acids Res 34:1-6 (corrected supplemental data from B. Wanner)
  2. ↑ 2.0 2.1 2.2 2.3 EcoCyc (release 10.6; 2007) Keseler, IM et al. (2005) Nucleic Acids Res. 33(Database issue):D334-7
  3. ↑ 3.0 3.1 EcoCyc (release 11.1; 2007) Keseler, IM et al. (2005) Nucleic Acids Res. 33(Database issue):D334-7
  4. ↑ EcoGene: Rudd, KE (2000) EcoGene: a genome sequence database for Escherichia coli K-12. Nucleic Acids Res 28:60-4.
  5. ↑ 5.0 5.1 5.2 Glickman, BW & Radman, M (1980) Escherichia coli mutator mutants deficient in methylation-instructed DNA mismatch correction. Proc. Natl. Acad. Sci. U.S.A. 77 1063-7 PubMed
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Ban, C & Yang, W (1998) Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis. Cell 95 541-52 PubMed
  7. ↑ Lahue, RS et al. (1989) DNA mismatch correction in a defined system. Science 245 160-4 PubMed
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 Junop, MS et al. (2003) In vitro and in vivo studies of MutS, MutL and MutH mutants: correlation of mismatch repair and DNA recombination. DNA Repair (Amst.) 2 387-405 PubMed
  9. ↑ Rayssiguier, C et al. (1989) The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature 342 396-401 PubMed
  10. ↑ 10.0 10.1 10.2 Butland, G et al. (2005) Interaction network containing conserved and essential protein complexes in Escherichia coli. Nature 433 531-7 PubMed
  11. ↑ Hu, P et al. (2009) Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins. PLoS Biol. 7 e96 PubMed
  12. ↑ Polosina, YY et al. (2009) The Escherichia coli mismatch repair protein MutL recruits the Vsr and MutH endonucleases in response to DNA damage. J. Bacteriol. 191 4041-3 PubMed
  13. ↑ López de Saro, FJ et al. (2006) The beta sliding clamp binds to multiple sites within MutL and MutS. J. Biol. Chem. 281 14340-9 PubMed
  14. ↑ Allen, DJ et al. (1997) MutS mediates heteroduplex loop formation by a translocation mechanism. EMBO J. 16 4467-76 PubMed
  15. ↑ 15.0 15.1 Hall, MC & Matson, SW (1999) The Escherichia coli MutL protein physically interacts with MutH and stimulates the MutH-associated endonuclease activity. J. Biol. Chem. 274 1306-12 PubMed
  16. ↑ Hall, MC et al. (1998) Evidence for a physical interaction between the Escherichia coli methyl-directed mismatch repair proteins MutL and UvrD. EMBO J. 17 1535-41 PubMed
  17. ↑ Zhang, M et al. (2012) MutL associates with Escherichia coli RecA and inhibits its ATPase activity. Arch. Biochem. Biophys. 517 98-103 PubMed
  18. ↑ 18.0 18.1 18.2 Finn, RD et al. (2010) The Pfam protein families database. Nucleic Acids Res. 38 D211-22 PubMed
  19. ↑ Feng, G & Winkler, ME (1995) Single-step purifications of His6-MutH, His6-MutL and His6-MutS repair proteins of escherichia coli K-12. BioTechniques 19 956-65 PubMed

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