CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007402
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
 COCA2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
33QRPANAIKEMIENCLubiquitination[1]
57IVKEGGLKLIQIQDNubiquitination[1]
70DNGTGIRKEDLDIVCubiquitination[1]
84CERFTTSKLQSFEDLubiquitination[1]
136SYSDGKLKAPPKPCAubiquitination[1]
164YNIATRRKALKNPSEubiquitination[1]
167ATRRKALKNPSEEYGubiquitination[1]
175NPSEEYGKILEVVGRubiquitination[1]
196GISFSVKKQGETVADubiquitination[1]
333VQQHIESKLLGSNSSubiquitination[1]
377STSGSSDKVYAHQMVubiquitination[1]
453SLEGDTTKGTSEMSEubiquitination[1]
488MVEDDSRKEMTAACTubiquitination[1]
688AMFYSIRKQYISEESubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
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. 
Sequence Annotation
 REGION 410 650 Interaction with EXO1.
 MOD_RES 477 477 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Cell cycle; Complete proteome; Disease mutation; DNA damage; DNA repair; Hereditary nonpolyposis colorectal cancer; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Tumor suppressor. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 756 AA 
Protein Sequence
MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTSIQVI VKEGGLKLIQ 60
IQDNGTGIRK EDLDIVCERF TTSKLQSFED LASISTYGFR GEALASISHV AHVTITTKTA 120
DGKCAYRASY SDGKLKAPPK PCAGNQGTQI TVEDLFYNIA TRRKALKNPS EEYGKILEVV 180
GRYSVHNAGI SFSVKKQGET VADVRTLPNA STVDNIRSIF GNAVSRELIE IGCEDKTLAF 240
KMNGYISNAN YSVKKCIFLL FINHRLVEST SLRKAIETVY AAYLPKNTHP FLYLSLEISP 300
QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEMV 360
KSTTSLTSSS TSGSSDKVYA HQMVRTDSRE QKLDAFLQPL SKPLSSQPQA IVTEDKTDIS 420
SGRARQQDEE MLELPAPAEV AAKNQSLEGD TTKGTSEMSE KRGPTSSNPR KRHREDSDVE 480
MVEDDSRKEM TAACTPRRRI INLTSVLSLQ EEINEQGHEV LREMLHNHSF VGCVNPQWAL 540
AQHQTKLYLL NTTKLSEELF YQILIYDFAN FGVLRLSEPA PLFDLAMLAL DSPESGWTEE 600
DGPKEGLAEY IVEFLKKKAE MLADYFSLEI DEEGNLIGLP LLIDNYVPPL EGLPIFILRL 660
ATEVNWDEEK ECFESLSKEC AMFYSIRKQY ISEESTLSGQ QSEVPGSIPN SWKWTVEHIV 720
YKALRSHILP PKHFTEDGNI LQLANLPDLY KVFERC 756 
Gene Ontology
 GO:0005712; C:chiasma; IBA:RefGenome.
 GO:0001673; C:male germ cell nucleus; IEA:Compara.
 GO:0032389; C:MutLalpha complex; IBA:RefGenome.
 GO:0032390; C:MutLbeta complex; IBA:RefGenome.
 GO:0000795; C:synaptonemal complex; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:InterPro.
 GO:0016887; F:ATPase activity; IBA:RefGenome.
 GO:0032137; F:guanine/thymine mispair binding; IEA:Compara.
 GO:0006303; P:double-strand break repair via nonhomologous end joining; IEA:Compara.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Compara.
 GO:0045190; P:isotype switching; IEA:Compara.
 GO:0007060; P:male meiosis chromosome segregation; IEA:Compara.
 GO:0043060; P:meiotic metaphase I plate congression; IEA:Compara.
 GO:0006298; P:mismatch repair; IBA:RefGenome.
 GO:0045950; P:negative regulation of mitotic recombination; IEA:Compara.
 GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IEA:Compara.
 GO:0048477; P:oogenesis; IEA:Compara.
 GO:0007131; P:reciprocal meiotic recombination; IBA:RefGenome.
 GO:0000712; P:resolution of meiotic recombination intermediates; IEA:Compara.
 GO:0016446; P:somatic hypermutation of immunoglobulin genes; IBA:RefGenome.
 GO:0007283; P:spermatogenesis; IEA:Compara.
 GO:0051257; P:spindle midzone assembly involved in meiosis; IEA:Compara. 
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