mutL:Gene Product(s)

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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)


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Notes

Function

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<protect> 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

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

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<protect> 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)


Domains/Motifs/Modification Sites

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

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]

<motif_map/>

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

Structures

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

Models

View models at:

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Structure figures

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Notes

Gene Product Resources

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

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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See Help:Gene_accessions for help with entering information into the Gene Accessions table.

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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See Help:References for how to manage references in EcoliWiki.

  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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