CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-021810
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA mismatch repair protein Mlh1 
Protein Synonyms/Alias
 MutL protein homolog 1 
Gene Name
 Mlh1 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
377STSGSGDKVYAYQMVacetylation[1]
Reference
 [1] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441] 
Functional Description
 Heterodimerizes with Pms2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (Msh2-Msh6) or MutS beta (Msh2-Msh6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS- heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of Pms2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (Mlh1-Pms2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with Mlh3 to form MutL gamma which plays a role in meiosis (By similarity). 
Sequence Annotation
 REGION 412 654 Interaction with EXO1 (By similarity).
 MOD_RES 481 481 Phosphoserine (By similarity).  
Keyword
 Cell cycle; Complete proteome; DNA damage; DNA repair; Nucleus; Phosphoprotein; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 760 AA 
Protein Sequence
MAFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTNIQVV VKEGGLKLIQ 60
IQDNGTGIRK EDLDIVCERF TTSKLQTFED LASISTYGFR GEALASISHV AHVTITTKTA 120
DGKCAYRASY SDGKLQAPPK PCAGNQGTLI TVEDLFYNII TRRKALKNPS EEYGKILEVV 180
GRYSIHNSGI SFSVKKQGET VSDVRTLPNA TTVDNIRSIF GNAVSRELIE VGCEDKTLAF 240
KMNGYISNAN YSVKKCIFLL FINHRLVESA ALRKAIETVY AAYLPKNTHP FLYLSLEISP 300
QNVDVNVHPT KHEVHFLHEE SILQRVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEAA 360
RPTTGVASSS TSGSGDKVYA YQMVRTDSRE QKLDAFLQPV SSLGPSQPQD PAPVRGARTE 420
GSPERATRED EEMLALPAPA EAAAESENLE RESLMETSDA AQKAAPTSSP GSSRKRHRED 480
SDVEMVENAS GKEMTAACYP RRRIINLTSV LSLQEEISER CHETLREMLR NHSFVGCVNP 540
QWALAQHQTK LYLLNTTKLS EELFYQILIY DFANFGVLRL SEPAPLFDLA MLALDSPESG 600
WTEDDGPKEG LAEYIVEFLK KKAEMLADYF SVEIDEEGNL IGLPLLIDSY VPPLEGLPIF 660
ILRLATEVNW DEEKECFESL SKECAMFYSI RKQYILEEST LSGQQSDMPG STSKPWKWTV 720
EHIIYKAFRS HLLPPKHFTE DGNVLQLANL PDLYKVFERC 760 
Gene Ontology
 GO:0005712; C:chiasma; IDA:MGI.
 GO:0001673; C:male germ cell nucleus; IDA:MGI.
 GO:0032389; C:MutLalpha complex; IDA:MGI.
 GO:0032390; C:MutLbeta complex; IBA:RefGenome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0000795; C:synaptonemal complex; IDA:MGI.
 GO:0005524; F:ATP binding; IEA:InterPro.
 GO:0016887; F:ATPase activity; IBA:RefGenome.
 GO:0032137; F:guanine/thymine mispair binding; IGI:MGI.
 GO:0032407; F:MutSalpha complex binding; IBA:RefGenome.
 GO:0003697; F:single-stranded DNA binding; IBA:RefGenome.
 GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:MGI.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
 GO:0045190; P:isotype switching; IMP:MGI.
 GO:0007060; P:male meiosis chromosome segregation; IMP:MGI.
 GO:0043060; P:meiotic metaphase I plate congression; IMP:MGI.
 GO:0006298; P:mismatch repair; IDA:MGI.
 GO:0045950; P:negative regulation of mitotic recombination; IMP:MGI.
 GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IMP:MGI.
 GO:0048477; P:oogenesis; IMP:MGI.
 GO:0000712; P:resolution of meiotic recombination intermediates; IMP:MGI.
 GO:0016446; P:somatic hypermutation of immunoglobulin genes; IMP:MGI.
 GO:0007283; P:spermatogenesis; IMP:MGI.
 GO:0051257; P:spindle midzone assembly involved in meiosis; IMP:MGI.
 GO:0007129; P:synapsis; IMP:MGI. 
Interpro
 IPR002099; DNA_mismatch_repair.
 IPR013507; DNA_mismatch_repair_C.
 IPR014762; DNA_mismatch_repair_CS.
 IPR011186; DNA_mismatch_repair_MLH1.
 IPR014763; DNA_mismatch_repair_N.
 IPR003594; HATPase_ATP-bd.
 IPR020568; Ribosomal_S5_D2-typ_fold.
 IPR014721; Ribosomal_S5_D2-typ_fold_subgr. 
Pfam
 PF01119; DNA_mis_repair 
SMART
 SM00387; HATPase_c 
PROSITE
 PS00058; DNA_MISMATCH_REPAIR_1 
PRINTS