MLH1
entrez
4292
canonical
uniprot
P40692
canonical
ensembl
ENSG00000076242
resolver
ensp
ENSP00000231790
resolver
ensp
ENSP00000398272
resolver
ensp
ENSP00000402564
resolver
ensp
ENSP00000402667
resolver
ensp
ENSP00000416687
resolver
ensp
ENSP00000443665
resolver
ensp
ENSP00000444286
resolver
ensp
ENSP00000480669
resolver
ensp
ENSP00000500979
resolver
ensp
ENSP00000501081
resolver
ensp
ENSP00000518393
resolver
ensp
ENSP00000518946
resolver
ensp
ENSP00000518979
resolver
ensp
ENSP00000519108
resolver
ensp
ENSP00000646173
resolver
enst
ENST00000456676
resolver
enst
ENST00000616768
resolver
enst
ENST00000673673
resolver
enst
ENST00000673990
resolver
enst
ENST00000713802
resolver
genesymbol
MLH1
resolver
genesymbol_syn
COCA2
resolver
hgnc
HGNC:7127
resolver
uniprot
A0A087WX20
resolver
uniprot
A0A669KAW3
resolver
uniprot
A0AAQ5BGN3
resolver
uniprot
A0AAQ5BGZ2
resolver
uniprot
B4DI13
resolver
uniprot
B4DQ11
resolver
uniprot
E9PCU2
resolver
uniprot
H0Y818
resolver
uniprot
Q59EG3
resolver
uniprot_entry
A0A087WX20_HUMAN
resolver
uniprot_entry
A0A669KAW3_HUMAN
resolver
uniprot_entry
A0AAQ5BGN3_HUMAN
resolver
uniprot_entry
A0AAQ5BGZ2_HUMAN
resolver
uniprot_entry
H0Y818_HUMAN
resolver
uniprot_entry
MLH1_HUMAN
resolver
uniprot_entry
Q59EG3_HUMAN
resolver
uniprot_sec
B4DI13
resolver
uniprot_sec
B4DQ11
resolver
uniprot_sec
E9PCU2
resolver
amino_acid_sequence
MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGKLKAPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVVGRYSVHNAGISFSVKKQGETVADVRTLPNASTVDNIRSIFGNAVSRELIEIGCEDKTLAFKMNGYISNANYSVKKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKLLGSNSSRMYFTQTLLPGLAGPSGEMVKSTTSLTSSSTSGSSDKVYAHQMVRTDSREQKLDAFLQPLSKPLSSQPQAIVTEDKTDISSGRARQQDEEMLELPAPAEVAAKNQSLEGDTTKGTSEMSEKRGPTSSNPRKRHREDSDVEMVEDDSRKEMTAACTPRRRIINLTSVLSLQEEINEQGHEVLREMLHNHSFVGCVNPQWALAQHQTKLYLLNTTKLSEELFYQILIYDFANFGVLRLSEPAPLFDLAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAEMLADYFSLEIDEEGNLIGLPLLIDNYVPPLEGLPIFILRLATEVNWDEEKECFESLSKECAMFYSIRKQYISEESTLSGQQSEVPGSIPNSWKWTVEHIVYKALRSHILPPKHFTEDGNILQLANLPDLYKVFERC
uniprot
proteins
disease_involvement
DISEASE: Lynch syndrome 2 (LYNCH2) [MIM:609310]: A form of Lynch syndrome, an autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. Lynch syndrome is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, it is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical Lynch syndrome is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected Lynch syndrome' or 'incomplete Lynch syndrome' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. {ECO:0000269|PubMed:10323887, ECO:0000269|PubMed:10375096, ECO:0000269|PubMed:10386556, ECO:0000269|PubMed:10413423, ECO:0000269|PubMed:10480359, ECO:0000269|PubMed:10598809, ECO:0000269|PubMed:10627141, ECO:0000269|PubMed:10660333, ECO:0000269|PubMed:10671064, ECO:0000269|PubMed:10713887, ECO:0000269|PubMed:10777691, ECO:0000269|PubMed:10882759, ECO:0000269|PubMed:11139242, ECO:0000269|PubMed:11427529, ECO:0000269|PubMed:11726306, ECO:0000269|PubMed:11748856, ECO:0000269|PubMed:11754112, ECO:0000269|PubMed:11781295, ECO:0000269|PubMed:11793442, ECO:0000269|PubMed:11839723, ECO:0000269|PubMed:11870161, ECO:0000269|PubMed:12095971, ECO:0000269|PubMed:12132870, ECO:0000269|PubMed:12200596, ECO:0000269|PubMed:12362047, ECO:0000269|PubMed:12373605, ECO:0000269|PubMed:12655562, ECO:0000269|PubMed:12658575, ECO:0000269|PubMed:14635101, ECO:0000269|PubMed:14961575, ECO:0000269|PubMed:15064764, ECO:0000269|PubMed:15139004, ECO:0000269|PubMed:15365995, ECO:0000269|PubMed:15365996, ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:16451135, ECO:0000269|PubMed:17301300, ECO:0000269|PubMed:17510385, ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075, ECO:0000269|PubMed:7757073, ECO:0000269|PubMed:8521398, ECO:0000269|PubMed:8566964, ECO:0000269|PubMed:8571956, ECO:0000269|PubMed:8574961, ECO:0000269|PubMed:8797773, ECO:0000269|PubMed:8872463, ECO:0000269|PubMed:8993976, ECO:0000269|PubMed:9048925, ECO:0000269|PubMed:9067757, ECO:0000269|PubMed:9218993, ECO:0000269|PubMed:9272156, ECO:0000269|PubMed:9298827, ECO:0000269|PubMed:9311737, ECO:0000269|PubMed:9326924, ECO:0000269|PubMed:9399661, ECO:0000269|PubMed:9559627, ECO:0000269|PubMed:9718327, ECO:0000269|PubMed:9833759, ECO:0000269|PubMed:9927034, ECO:0000269|Ref.5}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mismatch repair cancer syndrome 1 (MMRCS1) [MIM:276300]: An autosomal recessive form of mismatch repair cancer syndrome, a childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. {ECO:0000269|PubMed:11427529, ECO:0000269|PubMed:17440981, ECO:0000269|PubMed:7661930}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy. {ECO:0000269|PubMed:8751876}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=Defects in MLH1 may contribute to lobular carcinoma in situ (LCIS), a non-invasive neoplastic disease of the breast.; DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Note=Some epigenetic changes can be transmitted unchanged through the germline (termed 'epigenetic inheritance'). Evidence that this mechanism occurs in humans is provided by the identification of individuals in whom 1 allele of the MLH1 gene is epigenetically silenced throughout the soma (implying a germline event). These individuals are affected by Lynch syndrome but does not have identifiable mutations in MLH1, even though it is silenced, which demonstrates that an epimutation can phenocopy a genetic disease.; DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:10598809, ECO:0000269|PubMed:10882759, ECO:0000269|PubMed:12132870, ECO:0000269|PubMed:12655564, ECO:0000269|PubMed:14504054, ECO:0000269|PubMed:18033691, ECO:0000269|PubMed:8872463, ECO:0000269|PubMed:9032648, ECO:0000269|PubMed:9087566, ECO:0000269|PubMed:9611074}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: 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-MSH3) 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. {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974, ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:39032648, ECO:0000269|PubMed:9311737}.
uniprot
proteins
mass_dalton
84601
uniprot
proteins
mutagenesis
MUTAGEN 33; /note="K->Q: Abolishes acetylation; when associated with Q-241, Q-361 and Q-377."; /evidence="ECO:0000269|PubMed:30770470"; MUTAGEN 33; /note="K->R: Abolishes acetylation and binding affinity for MSH6 and MSH2; when associated with R-241, R-361 and R-377."; /evidence="ECO:0000269|PubMed:30770470"; MUTAGEN 241; /note="K->Q: Abolishes acetylation; when associated with Q-33, Q-361 and Q-377."; /evidence="ECO:0000269|PubMed:30770470"; MUTAGEN 241; /note="K->R: Abolishes acetylation and binding affinity for MSH6 and MSH2; when associated with R-33, R-361 and R-377."; /evidence="ECO:0000269|PubMed:30770470"; MUTAGEN 361; /note="K->Q: Abolishes acetylation; when associated with Q-33, Q-241 and Q-377."; /evidence="ECO:0000269|PubMed:30770470"; MUTAGEN 361; /note="K->R: Abolishes acetylation and binding affinity for MSH6 and MSH2; when associated with R-33, R-241 and R-377."; /evidence="ECO:0000269|PubMed:30770470"; MUTAGEN 377; /note="K->Q: Abolishes acetylation; when associated with Q-33, Q-241 and Q-361."; /evidence="ECO:0000269|PubMed:30770470"; MUTAGEN 377; /note="K->R: Abolishes acetylation and binding affinity for MSH6 and MSH2; when associated with R-33, R-241 and R-361."; /evidence="ECO:0000269|PubMed:30770470"; MUTAGEN 471; /note="K->N: Affects binding to importins alpha, including KPNA2, hence may affect import to the nucleus."; /evidence="ECO:0000269|PubMed:29175432"; MUTAGEN 472; /note="R->N: Affects binding to importins alpha, including KPNA2, hence may affect import to the nucleus."; /evidence="ECO:0000269|PubMed:29175432
uniprot
proteins
post_translational_modification
PTM: Acetylated (PubMed:30770470). Deacetylated by HDAC6 which prevents the MutL alpha complex, formed by the MLH1-PMS2 heterodimer, from being recruited to the MutS alpha complex, formed by the MSH2-MSH6 heterodimer, leading to tolerance of DNA damage (PubMed:30770470). {ECO:0000269|PubMed:30770470}.; PTM: Ubiquitinated by UBR4; leading to proteasomal degradation. This ubiquitination is counteracted by the deubiquitinase USP5. {ECO:0000269|PubMed:39032648}.
uniprot
proteins
protein_family
DNA mismatch repair MutL/HexB family
uniprot
proteins
pubmed
10097147
uniprot
proteins
pubmed
10323887
uniprot
proteins
pubmed
10375096
uniprot
proteins
pubmed
10386556
uniprot
proteins
pubmed
10413423
uniprot
proteins
pubmed
10480359
uniprot
proteins
pubmed
10573010
uniprot
proteins
pubmed
10598809
uniprot
proteins
pubmed
10627141
uniprot
proteins
pubmed
10660333
uniprot
proteins
pubmed
10671064
uniprot
proteins
pubmed
10713887
uniprot
proteins
pubmed
10777691
uniprot
proteins
pubmed
10783165
uniprot
proteins
pubmed
10882759
uniprot
proteins
pubmed
11139242
uniprot
proteins
pubmed
11369138
uniprot
proteins
pubmed
11389087
uniprot
proteins
pubmed
11427529
uniprot
proteins
pubmed
11429708
uniprot
proteins
pubmed
11555625
uniprot
proteins
pubmed
11726306
uniprot
proteins
pubmed
11748856
uniprot
proteins
pubmed
11754112
uniprot
proteins
pubmed
11781295
uniprot
proteins
pubmed
11793442
uniprot
proteins
pubmed
11839723
uniprot
proteins
pubmed
11870161
uniprot
proteins
pubmed
12095971
uniprot
proteins
pubmed
12115348
uniprot
proteins
pubmed
12132870
uniprot
proteins
pubmed
12200596
uniprot
proteins
pubmed
12362047
uniprot
proteins
pubmed
12373605
uniprot
proteins
pubmed
12414623
uniprot
proteins
pubmed
12655562
uniprot
proteins
pubmed
12655564
uniprot
proteins
pubmed
12658575
uniprot
proteins
pubmed
14504054
uniprot
proteins
pubmed
14635101
uniprot
proteins
pubmed
14676842
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14961575
uniprot
proteins
pubmed
15064764
uniprot
proteins
pubmed
15139004
uniprot
proteins
pubmed
15184898
uniprot
proteins
pubmed
15365995
uniprot
proteins
pubmed
15365996
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16083711
uniprot
proteins
pubmed
16188885
uniprot
proteins
pubmed
16451135
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
16873053
uniprot
proteins
pubmed
16873062
uniprot
proteins
pubmed
17301300
uniprot
proteins
pubmed
17440981
uniprot
proteins
pubmed
17510385
uniprot
proteins
pubmed
18033691
uniprot
proteins
pubmed
18157157
uniprot
proteins
pubmed
18206974
uniprot
proteins
pubmed
18561205
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20020535
uniprot
proteins
pubmed
20603073
uniprot
proteins
pubmed
21120944
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22753075
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26249686
uniprot
proteins
pubmed
26300262
uniprot
proteins
pubmed
28494185
uniprot
proteins
pubmed
29175432
uniprot
proteins
pubmed
30770470
uniprot
proteins
pubmed
39032648
uniprot
proteins
pubmed
7661930
uniprot
proteins
pubmed
7757073
uniprot
proteins
pubmed
7812952
uniprot
proteins
pubmed
8128251
uniprot
proteins
pubmed
8145827
uniprot
proteins
pubmed
8521398
uniprot
proteins
pubmed
8566964
uniprot
proteins
pubmed
8571956
uniprot
proteins
pubmed
8574961
uniprot
proteins
pubmed
8609062
uniprot
proteins
pubmed
8751876
uniprot
proteins
pubmed
8797773
uniprot
proteins
pubmed
8872463
uniprot
proteins
pubmed
8993976
uniprot
proteins
pubmed
9032648
uniprot
proteins
pubmed
9048925
uniprot
proteins
pubmed
9067757
uniprot
proteins
pubmed
9087566
uniprot
proteins
pubmed
9218993
uniprot
proteins
pubmed
9259192
uniprot
proteins
pubmed
9272156
uniprot
proteins
pubmed
9298827
uniprot
proteins
pubmed
9311737
uniprot
proteins
pubmed
9326924
uniprot
proteins
pubmed
9399661
uniprot
proteins
pubmed
9526167
uniprot
proteins
pubmed
9559627
uniprot
proteins
pubmed
9611074
uniprot
proteins
pubmed
9718327
uniprot
proteins
pubmed
9833759
uniprot
proteins
pubmed
9927034
uniprot
proteins
sequence_length
756
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11429708, ECO:0000269|PubMed:14676842, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075, ECO:0000269|PubMed:30770470}. Chromosome {ECO:0000269|PubMed:26300262}. Note=Recruited to chromatin in a MCM9-dependent manner. {ECO:0000269|PubMed:26300262}.
uniprot
proteins