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P40692 (MLH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 166. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
DNA mismatch repair protein Mlh1
Alternative name(s):
MutL protein homolog 1
Gene names
Name:MLH1
Synonyms:COCA2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length756 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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-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. Ref.17 Ref.18

Subunit structure

Heterodimer of MLH1 and PMS2 (MutL alpha), MLH1 and PMS1 (MutL beta) or MLH1 and MLH3 (MutL gamma). Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with MBD4. Interacts with EXO1 and MTMR15/FAN1. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.24

Subcellular location

Nucleus Ref.13 Ref.15.

Tissue specificity

Colon, lymphocytes, breast, lung, spleen, testis, prostate, thyroid, gall bladder and heart.

Involvement in disease

Hereditary non-polyposis colorectal cancer 2 (HNPCC2) [MIM:609310]: 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. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC 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 HNPCC 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 HNPCC' or 'incomplete HNPCC' 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.5 Ref.12 Ref.29 Ref.30 Ref.31 Ref.32 Ref.34 Ref.35 Ref.37 Ref.38 Ref.39 Ref.40 Ref.42 Ref.43 Ref.45 Ref.46 Ref.48 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.55 Ref.57 Ref.58 Ref.59 Ref.60 Ref.61 Ref.62 Ref.63 Ref.64 Ref.66 Ref.69 Ref.71 Ref.72 Ref.73 Ref.74 Ref.76 Ref.77 Ref.78 Ref.79 Ref.80 Ref.81 Ref.82 Ref.83 Ref.85 Ref.87 Ref.88 Ref.89 Ref.91 Ref.92 Ref.94 Ref.96 Ref.97 Ref.99 Ref.100 Ref.102

Mismatch repair cancer syndrome (MMRCS) [MIM:276300]: Autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.28 Ref.98

Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16

Defects in MLH1 may contribute to lobular carcinoma in situ (LCIS), a non-invasive neoplastic disease of the breast. Ref.67

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 variations affecting the gene represented in this entry.

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 HNPCC but does not have identifiable mutations in MLH1, even though it is silenced, which demonstrates that an epimutation can phenocopy a genetic disease.

Sequence similarities

Belongs to the DNA mismatch repair MutL/HexB family.

Ontologies

Keywords
   Biological processCell cycle
DNA damage
DNA repair
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Hereditary nonpolyposis colorectal cancer
Tumor suppressor
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from Biological aspect of Ancestor. Source: GOC

double-strand break repair via nonhomologous end joining

Inferred from electronic annotation. Source: Ensembl

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from electronic annotation. Source: Ensembl

isotype switching

Inferred from electronic annotation. Source: Ensembl

male meiosis chromosome segregation

Inferred from electronic annotation. Source: Ensembl

meiotic metaphase I plate congression

Inferred from electronic annotation. Source: Ensembl

mismatch repair

Inferred from genetic interaction PubMed 23603115. Source: MGI

negative regulation of mitotic recombination

Inferred from electronic annotation. Source: Ensembl

nuclear-transcribed mRNA poly(A) tail shortening

Inferred from electronic annotation. Source: Ensembl

oogenesis

Inferred from electronic annotation. Source: Ensembl

reciprocal meiotic recombination

Inferred from Biological aspect of Ancestor. Source: RefGenome

resolution of meiotic recombination intermediates

Inferred from electronic annotation. Source: Ensembl

somatic hypermutation of immunoglobulin genes

Inferred from Biological aspect of Ancestor. Source: RefGenome

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

spindle midzone assembly involved in meiosis

Inferred from electronic annotation. Source: Ensembl

synapsis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentMutLalpha complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

MutLbeta complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

chiasma

Inferred from Biological aspect of Ancestor. Source: RefGenome

male germ cell nucleus

Inferred from electronic annotation. Source: Ensembl

mismatch repair complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

nucleus

Inferred by curator PubMed 11809883. Source: HGNC

synaptonemal complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: InterPro

ATPase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

guanine/thymine mispair binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P40692-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P40692-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-241: Missing.
Isoform 3 (identifier: P40692-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-101: MSFVAGVIRR...ASISTYGFRG → MAF
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.27
Chain2 – 756755DNA mismatch repair protein Mlh1
PRO_0000178000

Regions

Region410 – 650241Interaction with EXO1

Amino acid modifications

Modified residue21N-acetylserine Ref.27
Modified residue4771Phosphoserine Ref.22 Ref.23 Ref.26

Natural variations

Alternative sequence1 – 241241Missing in isoform 2.
VSP_045201
Alternative sequence1 – 101101MSFVA…YGFRG → MAF in isoform 3.
VSP_047023
Natural variant181R → C in HNPCC2. Ref.87
VAR_022663
Natural variant191I → F in HNPCC2; unknown pathological significance. Ref.82
VAR_043383
Natural variant211A → V in HNPCC2. Ref.92
VAR_043384
Natural variant221G → A. Ref.101
Corresponds to variant rs41295280 [ dbSNP | Ensembl ].
VAR_038023
Natural variant251I → F in HNPCC2. Ref.60
VAR_043385
Natural variant281P → L in HNPCC2. Ref.42 Ref.57 Ref.82 Ref.96 Ref.97
VAR_004433
Natural variant291A → S in HNPCC2; unknown pathological significance; has no effect on ex vivo splicing assay. Ref.83 Ref.96
VAR_043386
Natural variant321I → V. Ref.5
Corresponds to variant rs2020872 [ dbSNP | Ensembl ].
VAR_014876
Natural variant351M → K in HNPCC2; unknown pathological significance. Ref.97
VAR_043387
Natural variant351M → N in MMRCS; requires 2 nucleotide substitutions. Ref.74 Ref.98
VAR_043388
Natural variant351M → R in HNPCC2.
VAR_004434
Natural variant371E → ELNH Found in an endometrial cancer sample; somatic mutation.
VAR_004435
Natural variant381N → H in HNPCC2. Ref.74
VAR_043389
Natural variant411D → G in HNPCC2. Ref.91
VAR_043390
Natural variant411D → H Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054522
Natural variant441S → F in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay; has no effect on ex vivo splicing assay. Ref.45
VAR_004436
Natural variant45 – 473TSI → CF in HNPCC2.
VAR_043391
Natural variant541G → E in CRC; sporadic; somatic mutation. Ref.36
VAR_012902
Natural variant621Q → K in HNPCC2; reduced repair efficiency in a yeast mismatch repair assay. Ref.34
VAR_004437
Natural variant631D → E in HNPCC2. Ref.96
VAR_043392
Natural variant641N → S in HNPCC2. Ref.34
VAR_004438
Natural variant671G → E in CRC. Ref.101
VAR_038024
Natural variant671G → R in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay; has no effect on ex vivo splicing assay. Ref.40 Ref.53 Ref.54 Ref.83 Ref.92 Ref.96 Ref.97 Ref.102
VAR_004439
Natural variant671G → W in HNPCC2. Ref.55 Ref.58
VAR_012903
Natural variant681I → N in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay. Ref.92
VAR_004440
Natural variant691R → K in HNPCC2; reduced repair efficiency in a mismatch repair assay. Ref.50
VAR_004441
Natural variant711Missing in HNPCC2. Ref.96
VAR_043393
Natural variant771C → R in HNPCC2 and CRC; sporadic; normal interaction with PMS2; loss of function in a mismatch repair assay. Ref.51 Ref.78 Ref.96 Ref.102
VAR_004442
Natural variant771C → Y in CRC; sporadic; early onset. Ref.44
VAR_012904
Natural variant801F → V in HNPCC2. Ref.69 Ref.96
VAR_012905
Natural variant841K → E in HNPCC2. Ref.57 Ref.96
VAR_012906
Natural variant931S → G Common polymorphism; normal interaction with PMS2; no functional alteration detected by an in vitro mismatch repair assay. Ref.52 Ref.78 Ref.96 Ref.101
Corresponds to variant rs41295282 [ dbSNP | Ensembl ].
VAR_004443
Natural variant981G → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054523
Natural variant1011G → D in HNPCC2; has no effect on ex vivo splicing assay. Ref.87 Ref.102
VAR_022664
Natural variant1011G → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054524
Natural variant1021E → K in HNPCC2; unknown pathological significance. Ref.99
VAR_043394
Natural variant1061S → R in gastric cancer; unknown pathological significance. Ref.66
VAR_043395
Natural variant1071I → R in HNPCC2; normal interaction with PMS2; loss of function in a mismatch repair assay. Ref.78 Ref.96
VAR_004444
Natural variant1091H → Q in gastric cancer; unknown pathological significance. Ref.66
VAR_043396
Natural variant1111A → V in HNPCC2; unknown pathological significance. Ref.62 Ref.97
VAR_012907
Natural variant1161T → K Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054525
Natural variant1171T → M in HNPCC2; fails to interact with PMS2 and EXO1; loss of function in a mismatch repair assay; has no effect on ex vivo splicing assay. Ref.13 Ref.30 Ref.58 Ref.74 Ref.76 Ref.80 Ref.82 Ref.97 Ref.102
VAR_004445
Natural variant1171T → R in HNPCC2; equivalent substitution in yeast causes loss of function in mismatch repair assay. Ref.54
VAR_004446
Natural variant1261Y → N Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
Corresponds to variant rs200076893 [ dbSNP | Ensembl ].
VAR_054526
Natural variant1281A → P in HNPCC2. Ref.37
VAR_012908
Natural variant1321D → H in CRC; sporadic; susceptibility to; ATPase function attenuated but not eliminated. Ref.95
Corresponds to variant rs28930073 [ dbSNP | Ensembl ].
VAR_022665
Natural variant1551L → R in HNPCC2. Ref.96
VAR_043397
Natural variant1821R → G in HNPCC2; incomplete. Ref.43 Ref.58
VAR_012909
Natural variant1821R → K in HNPCC2. Ref.87
VAR_022666
Natural variant1851V → G in HNPCC2; defective in a mismatch repair assay; has no effect on ex vivo splicing assay. Ref.76 Ref.96
VAR_004447
Natural variant1851V → L in HNPCC2; unknown pathological significance. Ref.83
VAR_043398
Natural variant1931S → P in HNPCC2. Ref.51
VAR_004448
Natural variant2131V → M Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.5 Ref.63 Ref.77 Ref.96 Ref.102
Corresponds to variant rs2308317 [ dbSNP | Ensembl ].
VAR_012910
Natural variant2151N → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054527
Natural variant2161I → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054528
Natural variant2171R → C in HNPCC2; unknown pathological significance; proficient in a mismatch repair assay. Ref.32 Ref.48 Ref.76 Ref.89
Corresponds to variant rs4986984 [ dbSNP | Ensembl ].
VAR_004449
Natural variant2171R → G.
VAR_020469
Natural variant2191I → V Common polymorphism; found in 37% of alleles. Ref.5 Ref.36 Ref.37 Ref.40 Ref.44 Ref.53 Ref.54 Ref.62 Ref.75 Ref.76 Ref.79 Ref.80 Ref.82 Ref.96
Corresponds to variant rs1799977 [ dbSNP | Ensembl ].
VAR_004450
Natural variant226 – 29570Missing in HNPCC2.
VAR_004452
Natural variant2261R → L in HNPCC2. Ref.30
VAR_004451
Natural variant2341E → G in HNPCC2; unknown pathological significance. Ref.66
VAR_043399
Natural variant2441G → D in HNPCC2; defective in a mismatch repair assay. Ref.37 Ref.76 Ref.83
VAR_012911
Natural variant2441G → V in CRC; sporadic; somatic mutation; unknown pathological significance. Ref.36
VAR_012912
Natural variant2471S → P in HNPCC2. Ref.80 Ref.96
VAR_043400
Natural variant2601L → F Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054529
Natural variant2601L → R in CRC. Ref.64
VAR_043401
Natural variant2621Missing in HNPCC2. Ref.53
VAR_012913
Natural variant2641H → Y in HNPCC2. Ref.61
VAR_043402
Natural variant2651R → C Associated with HNPCC2; results in partial exon 10 skipping on ex vivo splicing assay. Ref.102
VAR_054530
Natural variant2651R → H Rare polymorphism; associated with HNPCC2; slightly lower mismatch repair efficiency; results in partial exon 10 skipping on ex vivo splicing assay. Ref.35 Ref.56 Ref.76 Ref.102
VAR_012914
Natural variant2681E → G in CRC. Ref.47
VAR_012915
Natural variant2821A → G in HNPCC2. Ref.89
VAR_043403
Natural variant2921L → P in HNPCC2; unknown pathological significance. Ref.82 Ref.97
VAR_043404
Natural variant2951S → T in HNPCC2. Ref.43
VAR_012916
Natural variant3041D → V in HNPCC2. Ref.64
VAR_043405
Natural variant3091P → S. Ref.101
VAR_038025
Natural variant3201E → D Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054531
Natural variant3211S → I in HNPCC2; unknown pathological significance. Ref.66
VAR_043406
Natural variant325 – 3273Missing in colorectal cancer.
VAR_043407
Natural variant3251R → Q in CRC; sporadic; somatic mutation; unknown pathological significance. Ref.36
VAR_012917
Natural variant3261V → A in HNPCC2; proficient in a mismatch repair assay. Ref.56 Ref.76 Ref.102
Corresponds to variant rs63751049 [ dbSNP | Ensembl ].
VAR_004453
Natural variant3291H → P in HNPCC2. Ref.39 Ref.57 Ref.69 Ref.96
VAR_012918
Natural variant3301Missing in HNPCC2; results in weak exon 11 skipping on ex vivo splicing assay. Ref.96 Ref.102
VAR_043408
Natural variant3381N → S in HNPCC2. Ref.73
VAR_043409
Natural variant3791Y → C in HNPCC2. Ref.87
VAR_022667
Natural variant3841V → D Can be associated with HNPCC in some populations. Ref.33 Ref.49 Ref.62
VAR_004454
Natural variant3851R → C in HNPCC2; unknown pathological significance. Ref.77
VAR_043410
Natural variant3851R → P in HNPCC2; unknown pathological significance. Ref.56
VAR_043411
Natural variant4061S → N. Ref.36 Ref.56 Ref.101
Corresponds to variant rs41294980 [ dbSNP | Ensembl ].
VAR_012919
Natural variant4411A → T in HNPCC2. Ref.45 Ref.97
VAR_012920
Natural variant4431K → Q. Ref.96
Corresponds to variant rs34213726 [ dbSNP | Ensembl ].
VAR_043412
Natural variant4721R → I in CRC; unknown pathological significance. Ref.66
VAR_043413
Natural variant4741R → Q in HNPCC2; unknown pathological significance. Ref.99 Ref.102
VAR_043414
Natural variant4741R → W Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054532
Natural variant4851D → E in HNPCC2. Ref.54
VAR_043415
Natural variant4851D → H in HNPCC2; unknown pathological significance. Ref.66
VAR_043416
Natural variant4921A → T in HNPCC2 and CRC; sporadic. Ref.31
VAR_004455
Natural variant5061V → A in HNPCC2.
VAR_004456
Natural variant5391A → D Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054533
Natural variant5421Q → L in HNPCC2; type II; equivalent substitution in yeast causes loss of function in a mismatch repair assay. Ref.4 Ref.32 Ref.89
VAR_004457
Natural variant5421Q → P in HNPCC2. Ref.89
VAR_043417
Natural variant5491L → P in HNPCC2; has no effect on ex vivo splicing assay. Ref.32 Ref.89 Ref.102
VAR_012921
Natural variant5501L → P in HNPCC2. Ref.96
VAR_043418
Natural variant5511N → T in HNPCC2; has no effect on ex vivo splicing assay. Ref.43 Ref.53 Ref.102
VAR_012922
Natural variant5591L → R in HNPCC2. Ref.87
VAR_022668
Natural variant5651I → F in HNPCC2. Ref.53
VAR_012923
Natural variant5741L → P in HNPCC2; type I; abrogates interaction with EXO1. Ref.4 Ref.12 Ref.32 Ref.89
VAR_004458
Natural variant5781E → G in HNPCC2 and CRC. Ref.59
VAR_004459
Natural variant5821L → V in HNPCC2; type II. Ref.4
Corresponds to variant rs63751713 [ dbSNP | Ensembl ].
VAR_004460
Natural variant5851L → R Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054534
Natural variant5861A → P in HNPCC2. Ref.85
VAR_015689
Natural variant5881L → P in HNPCC2. Ref.62
VAR_012924
Natural variant5891A → D in HNPCC2. Ref.96
VAR_043419
Natural variant5961Missing in HNPCC2.
VAR_043420
Natural variant6011D → G in CRC; unknown pathological significance. Ref.86
VAR_043421
Natural variant6031P → R in HNPCC2; unknown pathological significance; has no effect on ex vivo splicing assay. Ref.69 Ref.73 Ref.102
Corresponds to variant rs35831931 [ dbSNP | Ensembl ].
VAR_012925
Natural variant6071L → H in LCIS and HNPCC2; unknown pathological significance; has no effect on ex vivo splicing assay; could determine an increased risk of colon cancer. Ref.63 Ref.67 Ref.77 Ref.101 Ref.102
Corresponds to variant rs41295284 [ dbSNP | Ensembl ].
VAR_012926
Natural variant6121Missing in HNPCC2. Ref.96
VAR_043422
Natural variant6161Missing in HNPCC2 and MMRCS; abrogates interaction with EXO1; has no effect on ex vivo splicing assay. Ref.12 Ref.28 Ref.29 Ref.31 Ref.34 Ref.35 Ref.58 Ref.87 Ref.92 Ref.96
VAR_004461
Natural variant6181K → A Common polymorphism; requires 2 nucleotide substitutions. Ref.34 Ref.59 Ref.63 Ref.69 Ref.74 Ref.80 Ref.81 Ref.96 Ref.101
Corresponds to variant rs35502531 [ dbSNP | Ensembl ].
VAR_004462
Natural variant6181K → R in colorectal cancer. Ref.84
Corresponds to variant rs63750449 [ dbSNP | Ensembl ].
VAR_043424
Natural variant6181K → T in HNPCC2; type II. Ref.4 Ref.31 Ref.56 Ref.73 Ref.77 Ref.96
VAR_004463
Natural variant6181Missing in HNPCC2. Ref.97
VAR_043423
Natural variant6191A → P Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054535
Natural variant6221L → H in HNPCC2. Ref.72
VAR_012927
Natural variant6231A → P in HNPCC2; unknown pathological significance. Ref.97
VAR_043425
Natural variant626 – 6272FS → ST in HNPCC2.
VAR_004464
Natural variant6311D → A in HNPCC2; unknown pathological significance. Ref.66
VAR_043426
Natural variant6351N → K in gastric cancer; unknown pathological significance. Ref.66
VAR_043427
Natural variant6361L → P in HNPCC2. Ref.89
VAR_043428
Natural variant6401P → L Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054536
Natural variant6401P → S in HNPCC2; has no effect on ex vivo splicing assay. Ref.89 Ref.102
VAR_043429
Natural variant6461Y → C in HNPCC2; unknown pathological significance. Ref.81 Ref.96
Corresponds to variant rs35045067 [ dbSNP | Ensembl ].
VAR_043430
Natural variant6481P → L in HNPCC2. Ref.69 Ref.96
VAR_012928
Natural variant6481P → S in HNPCC2; protein unstable but still functional in mismatch repair. Ref.77 Ref.88 Ref.96
VAR_022669
Natural variant6541P → L in HNPCC2. Ref.96
VAR_043431
Natural variant6551I → V Found in an endometrial cancer sample; also associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.75 Ref.102
Corresponds to variant rs55907433 [ dbSNP | Ensembl ].
VAR_043432
Natural variant6561F → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054537
Natural variant6571Missing in HNPCC2; unknown pathological significance. Ref.97
VAR_043433
Natural variant6591R → L in HNPCC2. Ref.12 Ref.63
VAR_012929
Natural variant6591R → P in HNPCC2; interacts only very weakly with PMS2; equivalent substitution in yeast causes almost complete loss of function in a mismatch repair assay; abrogates interaction with EXO1. Ref.34 Ref.78 Ref.96
VAR_004465
Natural variant6591R → Q. Ref.96
VAR_043434
Natural variant6621T → P in HNPCC2; unknown pathological significance. Ref.69 Ref.79
VAR_012930
Natural variant6661W → R Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.102
VAR_054538
Natural variant6811A → T in HNPCC2; unknown pathological significance; equivalent substitution in yeast does not affect mismatch repair; abrogates interaction with EXO1. Ref.12 Ref.82 Ref.96 Ref.97 Ref.101 Ref.102
VAR_004466
Natural variant6871R → W in HNPCC2; unknown pathological significance. Ref.72 Ref.82 Ref.97
VAR_012931
Natural variant6891Q → R in HNPCC; unknown pathological significance. Ref.69 Ref.101 Ref.102
VAR_012932
Natural variant7161V → M. Ref.53 Ref.56 Ref.69 Ref.80 Ref.96 Ref.101
Corresponds to variant rs35831931 [ dbSNP | Ensembl ].
VAR_012933
Natural variant7181H → Y in HNPCC2; unknown pathological significance. Ref.60 Ref.73 Ref.101
Corresponds to variant rs2020873 [ dbSNP | Ensembl ].
VAR_004467
Natural variant7191I → INVFHI in HNPCC2.
VAR_043435
Natural variant7241L → M in HNPCC2. Ref.89
VAR_043436
Natural variant7291L → V.
Corresponds to variant rs1800149 [ dbSNP | Ensembl ].
VAR_004468
Natural variant7491L → P in colorectal cancer. Ref.84
VAR_043437
Natural variant7511K → R in HNPCC2; unknown pathological significance. Ref.71 Ref.97 Ref.101
VAR_012934
Natural variant7551R → W in HNPCC; incomplete. Ref.58
VAR_012935

Experimental info

Sequence conflict3521L → H in BAG60773. Ref.6
Sequence conflict708 – 7114Missing in AAA85687. Ref.4

Secondary structure

.................................................................................... 756
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: C9231FC406C2CA20

FASTA75684,601
        10         20         30         40         50         60 
MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMIENCL DAKSTSIQVI VKEGGLKLIQ 

        70         80         90        100        110        120 
IQDNGTGIRK EDLDIVCERF TTSKLQSFED LASISTYGFR GEALASISHV AHVTITTKTA 

       130        140        150        160        170        180 
DGKCAYRASY SDGKLKAPPK PCAGNQGTQI TVEDLFYNIA TRRKALKNPS EEYGKILEVV 

       190        200        210        220        230        240 
GRYSVHNAGI SFSVKKQGET VADVRTLPNA STVDNIRSIF GNAVSRELIE IGCEDKTLAF 

       250        260        270        280        290        300 
KMNGYISNAN YSVKKCIFLL FINHRLVEST SLRKAIETVY AAYLPKNTHP FLYLSLEISP 

       310        320        330        340        350        360 
QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEMV 

       370        380        390        400        410        420 
KSTTSLTSSS TSGSSDKVYA HQMVRTDSRE QKLDAFLQPL SKPLSSQPQA IVTEDKTDIS 

       430        440        450        460        470        480 
SGRARQQDEE MLELPAPAEV AAKNQSLEGD TTKGTSEMSE KRGPTSSNPR KRHREDSDVE 

       490        500        510        520        530        540 
MVEDDSRKEM TAACTPRRRI INLTSVLSLQ EEINEQGHEV LREMLHNHSF VGCVNPQWAL 

       550        560        570        580        590        600 
AQHQTKLYLL NTTKLSEELF YQILIYDFAN FGVLRLSEPA PLFDLAMLAL DSPESGWTEE 

       610        620        630        640        650        660 
DGPKEGLAEY IVEFLKKKAE MLADYFSLEI DEEGNLIGLP LLIDNYVPPL EGLPIFILRL 

       670        680        690        700        710        720 
ATEVNWDEEK ECFESLSKEC AMFYSIRKQY ISEESTLSGQ QSEVPGSIPN SWKWTVEHIV 

       730        740        750 
YKALRSHILP PKHFTEDGNI LQLANLPDLY KVFERC 

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Isoform 2 [UniParc].

Checksum: DCD9320AB8E5ADF5
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FASTA51558,375
Isoform 3 [UniParc].

Checksum: C7ED5BB8A39DA389
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FASTA65873,837

References

« Hide 'large scale' references
[1]"Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer."
Bronner C.E., Baker S.M., Morrison P.T., Warren G., Smith L.G., Lescoe M.K., Kane M.F., Earibino C., Lipford J., Lindblom A., Tannergaard P., Bollag R.J., Godwin A.R., Ward D.C., Nordenskjoeld M., Fishel R., Kolodner R.D., Liskay R.M.
Nature 368:258-261(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Mutation of a mutL homolog in hereditary colon cancer."
Papadopoulos N., Nicolaides N.C., Wei Y.-F., Ruben S.M., Carter K.C., Rosen C.A., Haseltine W.A., Fleischmann R.D., Fraser C.M., Adams M.D., Venter J.C., Hamilton S.R., Petersen G.M., Watson P., Lynch H.T., Peltomaeki P., Mecklin J.-P., de la Chapelle A., Kinzler K.W., Vogelstein B.
Science 263:1625-1629(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Gall bladder.
[3]"Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutations."
Kolodner R.D., Hall N.R., Lipford J.R., Kane M.F., Morrison P., Finan P.J., Burn J., Chapman P., Earabino C., Merchant E., Bishop D.T.
Cancer Res. 55:242-248(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Genomic structure of human mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non-polyposis colorectal cancer (HNPCC)."
Han H.-J., Maruyama M., Baba S., Park J.-G., Nakamura Y.
Hum. Mol. Genet. 4:237-242(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HNPCC2 LEU-542; PRO-574; VAL-582 AND THR-618.
[5]NIEHS SNPs program
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HNPCC2 MET-213, VARIANTS VAL-32 AND VAL-219.
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
Tissue: Brain, Corpus callosum, Kidney and Substantia nigra.
[7]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[10]"BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures."
Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.
Genes Dev. 14:927-939(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF MLH1 AS MEMBER OF BASC.
[11]"MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1."
Bellacosa A., Cicchillitti L., Schepis F., Riccio A., Yeung A.T., Matsumoto Y., Golemis E.A., Genuardi M., Neri G.
Proc. Natl. Acad. Sci. U.S.A. 96:3969-3974(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MBD4.
[12]"The interaction of DNA mismatch repair proteins with human exonuclease I."
Schmutte C., Sadoff M.M., Shim K.-S., Acharya S., Fishel R.
J. Biol. Chem. 276:33011-33018(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EXO1 AND PMS2, CHARACTERIZATION OF VARIANTS HNPCC2 PRO-574; LYS-616 DEL; LEU-659 AND THR-681, CHARACTERIZATION OF VARIANT MMRCS LYS-616 DEL.
[13]"HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutLalpha and hMLH1-hEXO1 complexes."
Jaeger A.C., Rasmussen M., Bisgaard H.C., Singh K.K., Nielsen F.C., Rasmussen L.J.
Oncogene 20:3590-3595(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EXO1, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT MET-117.
[14]"Functional alterations of human exonuclease 1 mutants identified in atypical hereditary nonpolyposis colorectal cancer syndrome."
Sun X., Zheng L., Shen B.
Cancer Res. 62:6026-6030(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EXO1.
[15]"Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA."
Nielsen F.C., Jaeger A.C., Luetzen A., Bundgaard J.R., Rasmussen L.J.
Oncogene 23:1457-1468(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EXO1, SUBCELLULAR LOCATION.
[16]"The genetic basis of Muir-Torre syndrome includes the hMLH1 locus."
Bapat B., Xia L., Madlensky L., Mitri A., Tonin P., Narod S.A., Gallinger S.
Am. J. Hum. Genet. 59:736-739(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MRTES.
[17]"Endonucleolytic function of MutLalpha in human mismatch repair."
Kadyrov F.A., Dzantiev L., Constantin N., Modrich P.
Cell 126:297-308(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[18]"Direct visualization of asymmetric adenine nucleotide-induced conformational changes in MutL alpha."
Sacho E.J., Kadyrov F.A., Modrich P., Kunkel T.A., Erie D.A.
Mol. Cell 29:112-121(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"Human mismatch repair: reconstitution of a nick-directed bidirectional reaction."
Constantin N., Dzantiev L., Kadyrov F.A., Modrich P.
J. Biol. Chem. 280:39752-39761(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[20]"MutLalpha: at the cutting edge of mismatch repair."
Jiricny J.
Cell 126:239-241(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[21]"Mechanisms and functions of DNA mismatch repair."
Li G.M.
Cell Res. 18:85-98(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[22]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[23]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[24]"A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair."
Smogorzewska A., Desetty R., Saito T.T., Schlabach M., Lach F.P., Sowa M.E., Clark A.B., Kunkel T.A., Harper J.W., Colaiacovo M.P., Elledge S.J.
Mol. Cell 39:36-47(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MTMR15.
[25]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[28]"The molecular basis of Turcot's syndrome."
Hamilton S.R., Liu B., Parsons R.E., Papadopoulos N., Jen J., Powell S.M., Krush A.J., Berk T., Cohen Z., Tetu B., Burger P.C., Wood P.A., Taqi F., Booker S.V., Petersen G.M., Offerhaus G.J.A., Tersmette A.C., Giardiello F.M., Vogelstein B., Kinzler K.W.
N. Engl. J. Med. 332:839-847(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MMRCS LYS-616 DEL.
[29]"Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16."
Wijnen J., Khan P.M., Vasen H., Menko F., van der Klift H., van den Broek M., van Leeuwen-Cornelisse I., Nagengast F., Meijers-Heijboer E.J., Lindhout D., Griffioen G., Cats A., Kleibeuker J., Varesco L., Bertario L., Bisgaard M.-L., Mohr J., Kolodner R.D., Fodde R.
Am. J. Hum. Genet. 58:300-307(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 LYS-616 DEL.
[30]"CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutations."
Maliaka Y.K., Chudina A.P., Belev N.F., Alday P., Bochkov N.P., Buerstedde J.-M.
Hum. Genet. 97:251-255(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 MET-117 AND LEU-226.
[31]"Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer."
Moslein G., Tester D.J., Lindor N.M., Honchel R., Cunningham J.M., French A.J., Halling K.C., Schwab M., Goretzki P., Thibodeau S.N.
Hum. Mol. Genet. 5:1245-1252(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 LYS-616 DEL AND THR-618, VARIANT CRC THR-492.
[32]"Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary nonpolyposis colorectal cancer."
Han H.-J., Yuan Y., Ku J.-L., Oh J.-H., Won Y.-J., Kang K.J., Kim K.Y., Kim S., Kim C.Y., Kim J.-P., Oh N.-G., Lee K.H., Choe K.J., Nakamura Y., Park J.-G.
J. Natl. Cancer Inst. 88:1317-1319(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 CYS-217; LEU-542; PRO-549 AND PRO-574.
[33]"Mutational analysis of mismatch repair genes, hMLH1 and hMSH2, in sporadic endometrial carcinomas with microsatellite instability."
Kobayashi K., Matsushima M., Koi S., Saito H., Sagae S., Kudo R., Nakamura Y.
Jpn. J. Cancer Res. 87:141-145(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-ASN-HIS-37 INS AND ASP-384.
[34]"Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations."
Wijnen J., Khan P.M., Vasen H., van der Klift H., Mulder A., van Leeuwen-Cornelisse I., Bakker B., Losekoot M., Moeller P., Fodde R.
Am. J. Hum. Genet. 61:329-335(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 LYS-62; SER-64; LYS-616 DEL; ALA-618 AND PRO-659.
[35]"Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer."
Viel A., Genuardi M., Capozzi E., Leonardi F., Bellacosa A., Paravatou-Petsotas M., Pomponi M.G., Fornasarig M., Percesepe A., Roncucci L., Tamassia M.G., Benatti P., Ponz de Leon M., Valenti A., Covino M., Anti M., Foletto M., Boiocchi M., Neri G.
Genes Chromosomes Cancer 18:8-18(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 LYS-616 DEL, VARIANT HIS-265.
[36]"MSH2 and MLH1 mutations in sporadic replication error-positive colorectal carcinoma as assessed by two-dimensional DNA electrophoresis."
Wu Y., Nystroem-Lahti M., Osinga J., Looman M.W.G., Peltomaeki P., Aaltonen L.A., de la Chapelle A., Hofstra R.M.W., Buys C.H.C.M.
Genes Chromosomes Cancer 18:269-278(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CRC GLU-54; VAL-244 AND GLN-325, VARIANTS VAL-219 AND ASN-406.
[37]"Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes."
Pensotti V., Radice P., Presciuttini S., Calistri D., Gazzoli I., Grimalt Perez A.P., Mondini P., Buonsanti G., Sala P., Rossetti C., Ranzani G.N., Bertario L., Pierotti M.A.
Genes Chromosomes Cancer 19:135-142(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 PRO-128 AND ASP-244, VARIANT VAL-219.
[38]"Use of SSCP analysis to identify germline mutations in HNPCC families fulfilling the Amsterdam criteria."
Beck N.E., Tomlinson I.P.M., Homfray T., Frayling I., Hodgson S.V., Harocopos C.J., Bodmer W.F.
Hum. Genet. 99:219-224(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 626-SER-THR-627.
[39]"Hereditary nonpolyposis colorectal cancer: causative role of a germline missense mutation in the hMLH1 gene confirmed by the independent occurrence of the same somatic mutation in tumour tissue."
Wang Y., Friedl W., Lamberti C., Ruelfs C., Kruse R., Propping P.
Hum. Genet. 100:362-364(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 PRO-329.
[40]"Mutational analysis of the hMLH1 gene using an automated two-dimensional DNA typing system."
Sasaki S., Tokino T., Miyatsu T., Muto T., Nakamura Y.
Hum. Mutat. 9:164-171(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 ARG-67, VARIANT VAL-219.
[41]"Molecular basis of HNPCC: mutations of MMR genes."
Papadopoulos N., Lindblom A.
Hum. Mutat. 10:89-99(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[42]"Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline mutations in hMSH2 or hMLH1 genes."
Wehner M., Buschhausen L., Lamberti C., Kruse R., Caspari R., Propping P., Friedl W.
Hum. Mutat. 10:241-244(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 LEU-28.
[43]"Germline hMSH2 and hMLH1 gene mutations in incomplete HNPCC families."
Wang Q., Desseigne F., Lasset C., Saurin J.-C., Navarro C., Yagci T., Keser I., Bagci H., Luleci G., Gelen T., Chayvialle J.-A., Puisieux A., Ozturk M.
Int. J. Cancer 73:831-836(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 GLY-182; THR-295 AND THR-551.
[44]"Germline HNPCC gene variants have little influence on the risk for sporadic colorectal cancer."
Tomlinson I.P.M., Beck N.E., Homfray T., Harocopos C.J., Bodmer W.F.
J. Med. Genet. 34:39-42(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CRC TYR-77, VARIANT VAL-219.
[45]"A human compound heterozygote for two MLH1 missense mutations."
Hackman P., Tannergaerd P., Osei-Mensa S., Chen J., Kane M.F., Kolodner R.D., Lambert B., Hellgren D., Lindblom A.
Nat. Genet. 17:135-136(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 PHE-44 AND THR-441.
[46]"Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls."
Farrington S.M., Lin-Goerke J., Ling J., Wang Y., Burczak J.D., Robbins D.J., Dunlop M.G.
Am. J. Hum. Genet. 63:749-759(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2, VARIANTS.
[47]"DGGE screening of mutations in mismatch repair genes (hMSH2 and hMLH1) in 34 Swedish families with colorectal cancer."
Liu T., Wahlberg S., Rubio C., Holmberg E., Groenberg H., Lindblom A.
Clin. Genet. 53:131-135(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CRC GLY-268.
[48]"Germline mutations of hMLH1 and hMSH2 genes in patients with suspected hereditary nonpolyposis colorectal cancer and sporadic early-onset colorectal cancer."
Yuan Y., Han H.-J., Zheng S., Park J.-G.
Dis. Colon Rectum 41:434-440(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 CYS-217.
[49]"A novel missense mutation in the DNA mismatch repair gene hMLH1 present among East Asians but not among Europeans."
Wang Y., Friedl W., Lamberti C., Noethen M.M., Kruse R., Propping P.
Hum. Hered. 48:87-91(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASP-384, ASSOCIATION WITH HNPCC.
[50]"Four new mutations in the DNA mismatch repair gene MLH1 in colorectal cancers with microsatellite instability."
Herfarth K.K.-F., Ogunbiyi O.A., Moley J.F., Kodner I.J., Wells S.A. Jr., Goodfellow P.J.
Hum. Mutat. 12:73-73(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 LYS-69.
[51]"hMLH1 mutations in hereditary nonpolyposis colorectal cancer kindreds."
Panariello L., Scarano M.I., de Rosa M., Capasso L., Renda A., Riegler G., Rossi G.B., Salvatore F., Izzo P.
Hum. Mutat. 12:216-217(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 ARG-77 AND PRO-193.
[52]"Hereditary nonpolyposis colorectal cancer: identification of novel germline mutations in two kindreds not fulfilling the Amsterdam criteria."
Quaresima B., Grandinetti C., Baudi F., Tassone P., Barbieri V., Conforti S., Avvedimento E.V., Costanzo F., Venuta S.
Hum. Mutat. 12:433-433(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 GLY-93.
[53]"Excess of hMLH1 germline mutations in Swiss families with hereditary non-polyposis colorectal cancer."
Hutter P., Couturier A., Membrez V., Joris F., Sappino A.-P., Chappuis P.O.
Int. J. Cancer 78:680-684(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 ARG-67; ILE-262 DEL; THR-551; PHE-565 AND MET-716, VARIANT VAL-219.
[54]"Influence of selection criteria on mutation detection in patients with hereditary nonpolyposis colorectal cancer."
Heinimann K., Scott R.J., Buerstedde J.-M., Weber W., Siebold K., Attenhofer M., Mueller H., Dobbie Z.
Cancer 85:2512-2518(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 ARG-67; ARG-117 AND GLU-485, VARIANT VAL-219.
[55]"Neurofibromatosis and early onset of cancers in hMLH1-deficient children."
Wang Q., Lasset C., Desseigne F., Frappaz D., Bergeron C., Navarro C., Ruano E., Puisieux A.
Cancer Res. 59:294-297(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 TRP-67.
[56]"Assessment of pathogenicity criteria for constitutional missense mutations of the hereditary nonpolyposis colorectal cancer genes MLH1 and MSH2."
Genuardi M., Carrara S., Anti M., Ponz de Leon M., Viel A.
Eur. J. Hum. Genet. 7:778-782(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HIS-265; ALA-326; PRO-385; ASN-406; THR-618 AND MET-716.
[57]"Microsatellite instability, a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer."
Lamberti C., Kruse R., Ruelfs C., Caspari R., Wang Y., Jungck M., Mathiak M., Malayeri H.R.H., Friedl W., Sauerbruch T., Propping P.
Gut 44:839-843(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 LEU-28; GLU-84 AND PRO-329.
[58]"Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer."
Wang Q., Lasset C., Desseigne F., Saurin J.-C., Maugard C., Navarro C., Ruano E., Descos L., Trillet-Lenoir V., Bosset J.-F., Puisieux A.
Hum. Genet. 105:79-85(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 TRP-67; MET-117; GLY-182 AND LYS-616 DEL, VARIANT HNPCC TRP-755.
[59]"Missense mutations in hMLH1 associated with colorectal cancer."
Liu T., Tannergaerd P., Hackman P., Rubio C., Kressner U., Lindmark G., Hellgren D., Lambert B., Lindblom A.
Hum. Genet. 105:437-441(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CRC GLY-578, VARIANT HNPCC2 ALA-618.
[60]"Novel hMLH1 and hMSH2 germline mutations in African Americans with colorectal cancer."
Weber T.K., Chin H.-M., Rodriguez-Bigas M., Keitz B., Gilligan R., O'Malley L., Urf E., Diba N., Pazik J., Petrelli N.J.
JAMA 281:2316-2320(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 PHE-25, VARIANT TYR-718.
[61]"Frequent microsatellite instability and mismatch repair gene mutations in young Chinese patients with colorectal cancer."
Chan T.L., Yuen S.T., Chung L.P., Ho J.W.C., Kwan K.Y.M., Chan A.S.Y., Ho J.C.Y., Leung S.Y., Wyllie A.H.
J. Natl. Cancer Inst. 91:1221-1226(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 TYR-264.
[62]"Enhanced detection of deleterious and other germline mutations of hMSH2 and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds."
Nomura S., Sugano K., Kashiwabara H., Taniguchi T., Fukayama N., Fujita S., Akasu T., Moriya Y., Ohhigashi S., Kakizoe T., Sekiya T.
Biochem. Biophys. Res. Commun. 271:120-129(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 VAL-111 AND PRO-588, VARIANTS VAL-219 AND ASP-384.
[63]"Detection of mutations in mismatch repair genes in Portuguese families with hereditary non-polyposis colorectal cancer (HNPCC) by a multi-method approach."
Fidalgo P., Almeida M.R., West S., Gaspar C., Maia L., Wijnen J., Albuquerque C., Curtis A., Cravo M., Fodde R., Leitao C.N., Burn J.
Eur. J. Hum. Genet. 8:49-53(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 MET-213; HIS-607; ALA-618 AND LEU-659.
[64]"Mutational germline analysis of hMSH2 and hMLH1 genes in early onset colorectal cancer patients."
Montera M., Resta N., Simone C., Guanti G., Marchese C., Civitelli S., Mancini A., Pozzi S., De Salvo L., Bruzzone D., Donadini A., Romio L., Mareni C.
J. Med. Genet. 37:E7-E7(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CRC ARG-260, VARIANT HNPCC2 VAL-304.
[65]Erratum
Montera M., Resta N., Simone C., Guanti G., Marchese C., Civitelli S., Mancini A., Pozzi S., De Salvo L., Bruzzone D., Donadini A., Romio L., Mareni C.
J. Med. Genet. 40:472-472(2003)
[66]"hMLH1 and hMSH2 mutations in families with familial clustering of gastric cancer and hereditary non-polyposis colorectal cancer."
Kim J.C., Kim H.C., Roh S.A., Koo K.H., Lee D.H., Yu C.S., Lee J.H., Kim T.W., Lee H.I., Beck N.E., Bodmer W.F.
Cancer Detect. Prev. 25:503-510(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GASTRIC CANCER ARG-106; GLN-109 AND LYS-635, VARIANTS HNPCC2 GLY-234; ILE-321; HIS-485 AND ALA-631, VARIANT CRC ILE-472.
[67]"Contribution of germline MLH1 and MSH2 mutations to lobular carcinoma in situ of the breast."
Stone J.G., Coleman G., Gusterson B., Marossy A., Lakhani S.R., Ward A., Nash A., McKinna A., A'Hern R., Stratton M.R., Houlston R.S.
Cancer Lett. 167:171-174(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LCIS HIS-607.
[68]"Extensive somatic microsatellite mutations in normal human tissue."
Vilkki S., Tsao J.-L., Loukola A., Poyhonen M., Vierimaa O., Herva R., Aaltonen L.A., Shibata D.
Cancer Res. 61:4541-4544(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN TUMORIGENESIS.
[69]"Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer) patients: mutations or polymorphisms?"
Mueller-Koch Y., Kopp R., Lohse P., Baretton G., Stoetzer A., Aust D., Daum J., Kerker B., Gross M., Dietmeier W., Holinski-Feder E.
Eur. J. Med. Res. 6:473-482(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 VAL-80; PRO-329; ARG-603; ALA-618; LEU-648; PRO-662 AND MET-716, VARIANT HNPCC ARG-689.
[70]"Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae."
Ellison A.R., Lofing J., Bitter G.A.
Hum. Mol. Genet. 10:1889-1900(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS.
[71]"Optimization of experimental conditions for RNA-based sequencing of MLH1 and MSH2 genes."
Jakubowska A., Gorski B., Kurzawski G., Debniak T., Hadaczek P., Cybulski C., Kladny J., Oszurek O., Scott R.J., Lubinski J.
Hum. Mutat. 17:52-60(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 ARG-751.
[72]"Eight novel germline MLH1 and MSH2 mutations in hereditary non-polyposis colorectal cancer families from Spain."
Godino J., de La Hoya M., Diaz-Rubio E., Benito M., Caldes T.
Hum. Mutat. 18:549-549(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 HIS-622 AND TRP-687.
[73]"hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer."
Rossi B.M., Lopes A., Oliveira Ferreira F., Nakagawa W.T., Napoli Ferreira C.C., Casali Da Rocha J.C., Simpson C.C., Simpson A.J.G.
Ann. Surg. Oncol. 9:555-561(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 SER-338; ARG-603; THR-618 AND TYR-718.
[74]"Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach."
Gille J.J.P., Hogervorst F.B.L., Pals G., Wijnen J.T., van Schooten R.J., Dommering C.J., Meijer G.A., Craanen M.E., Nederlof P.M., de Jong D., McElgunn C.J., Schouten J.P., Menko F.H.
Br. J. Cancer 87:892-897(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 ASN-35; HIS-38; MET-117 AND ALA-618.
[75]"Microsatellite instability and mutation analysis of candidate genes in unselected Sardinian patients with endometrial carcinoma."
Baldinu P., Cossu A., Manca A., Satta M.P., Pisano M., Casula M., Dessole S., Pintus A., Tanda F., Palmieri G.
Cancer 94:3157-3168(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-219 AND VAL-655.
[76]"Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system."
Trojan J., Zeuzem S., Randolph A., Hemmerle C., Brieger A., Raedle J., Plotz G., Jiricny J., Marra G.
Gastroenterology 122:211-219(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS HNPCC2 MET-117; GLY-185; CYS-217; ASP-244 AND ALA-326, CHARACTERIZATION OF VARIANTS VAL-219 AND HIS-265.
[77]"Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1 mismatch repair genes: implications for genetic testing."
Cravo M., Afonso A.J., Lage P., Albuquerque C., Maia L., Lacerda C., Fidalgo P., Chaves P., Cruz C., Nobre-Leitao C.
Gut 50:405-412(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 CYS-385; HIS-607; THR-618 AND SER-648, VARIANT MET-213.
[78]"Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer."
Nystroem-Lahti M., Perrera C., Raeschle M., Panyushkina-Seiler E., Marra G., Curci A., Quaresima B., Costanzo F., D'Urso M., Venuta S., Jiricny J.
Genes Chromosomes Cancer 33:160-167(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS HNPCC2 ARG-77; GLY-93; ARG-107 AND PRO-659.
[79]"Seven novel MLH1 and MSH2 germline mutations in hereditary nonpolyposis colorectal cancer."
Krueger S., Plaschke J., Pistorius S., Jeske B., Haas S., Kraemer H., Hinterseher I., Bier A., Kreuz F.R., Theissig F., Saeger H.D., Schackert H.K.
Hum. Mutat. 19:82-82(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 PRO-662, VARIANT VAL-219.
[80]"Impact of microsatellite testing and mismatch repair protein expression on the clinical interpretation of genetic testing in hereditary non-polyposis colorectal cancer."
Ward R., Meldrum C., Williams R., Mokany E., Scott R., Turner J., Hawkins N., Burgess B., Groombridge C., Spigelman A.
J. Cancer Res. Clin. Oncol. 128:403-411(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 MET-117 AND PRO-247, VARIANTS VAL-219; ALA-618 AND MET-716.
[81]"Mutations of hMLH1 and hMSH2 in patients with suspected hereditary nonpolyposis colorectal cancer: correlation with microsatellite instability and abnormalities of mismatch repair protein expression."
Scartozzi M., Bianchi F., Rosati S., Galizia E., Antolini A., Loretelli C., Piga A., Bearzi I., Cellerino R., Porfiri E.
J. Clin. Oncol. 20:1203-1208(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 CYS-646, VARIANT ALA-618.
[82]"Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States."
Kurzawski G., Suchy J., Kladny J., Safranow K., Jakubowska A., Elsakov P., Kucinskas V., Gardovski J., Irmejs A., Sibul H., Huzarski T., Byrski T., Debniak T., Cybulski C., Gronwald J., Oszurek O., Clark J., Gozdz S. expand/collapse author list , Niepsuj S., Slomski R., Plawski A., Lacka-Wojciechowska A., Rozmiarek A., Fiszer-Maliszewska L., Bebenek M., Sorokin D., Stawicka M., Godlewski D., Richter P., Brozek I., Wysocka B., Jawien A., Banaszkiewicz Z., Kowalczyk J., Czudowska D., Goretzki P.E., Moeslein G., Lubinski J.
J. Med. Genet. 39:E65-E65(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 PHE-19; LEU-28; MET-117; PRO-292; THR-681 AND TRP-687, VARIANT VAL-219.
[83]"Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene."
Wagner A., Barrows A., Wijnen J.T., van der Klift H., Franken P.F., Verkuijlen P., Nakagawa H., Geugien M., Jaghmohan-Changur S., Breukel C., Meijers-Heijboer H., Morreau H., van Puijenbroek M., Burn J., Coronel S., Kinarski Y., Okimoto R., Watson P. expand/collapse author list , Lynch J.F., de la Chapelle A., Lynch H.T., Fodde R.
Am. J. Hum. Genet. 72:1088-1100(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 SER-29; ARG-67; LEU-185 AND ASP-244.
[84]"Microsatellite instability and mutation analysis among southern Italian patients with colorectal carcinoma: detection of different alterations accounting for MLH1 and MSH2 inactivation in familial cases."
Colombino M., Cossu A., Arba A., Manca A., Curci A., Avallone A., Comella G., Botti G., Scintu F., Amoruso M., D'Abbicco D., d'Agnessa M.R., Spanu A., Tanda F., Palmieri G.
Ann. Oncol. 14:1530-1536(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS COLORECTAL CANCER 325-ARG--GLN-327 DEL; ARG-618 AND PRO-749.
[85]"Identification of six novel MSH2 and MLH1 germline mutations in HNPCC."
Kruger S., Plaschke J., Jeske B., Gorgens H., Pistorius S.R., Bier A., Kreuz F.R., Theissig F., Aust D.E., Saeger H.D., Schackert H.K.
Hum. Mutat. 21:445-446(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 PRO-586.
[86]"Genetic analysis of familial colorectal cancer in Israeli Arabs."
Chen-Shtoyerman R., Theodor L., Harmati E., Friedman E., Dacka S., Kopelman Y., Sternberg A., Zarivach R., Bar-Meir S., Fireman Z.
Hum. Mutat. 21:446-447(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CRC GLY-601.
[87]"Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA."
Taylor C.F., Charlton R.S., Burn J., Sheridan E., Taylor G.R.
Hum. Mutat. 22:428-433(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 CYS-18; ASP-101; LYS-182; CYS-379; ARG-559 AND LYS-616 DEL.
[88]"HNPCC mutation MLH1 P648S makes the functional protein unstable, and homozygosity predisposes to mild neurofibromatosis type 1."
Raevaara T.E., Gerdes A.-M., Loennqvist K.E., Tybjaerg-Hansen A., Abdel-Rahman W.M., Kariola R., Peltomaeki P., Nystroem-Lahti M.
Genes Chromosomes Cancer 40:261-265(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 SER-648.
[89]"Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families."
Shin Y.-K., Heo S.-C., Shin J.-H., Hong S.-H., Ku J.-L., Yoo B.-C., Kim I.-J., Park J.-G.
Hum. Mutat. 24:351-351(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 CYS-217; GLY-282; LEU-542; PRO-542; PRO-549; PRO-574; PRO-636; SER-640 AND MET-724.
[90]Erratum
Shin Y.K., Heo S.C., Shin J.H., Hong S.H., Ku J.L., Yoo B.C., Kim I.J., Park J.G.
Hum. Mutat. 25:224-224(2005)
[91]"Ten novel MSH2 and MLH1 germline mutations in families with HNPCC."
Krueger S., Bier A., Plaschke J., Hoehl R., Aust D.E., Kreuz F.R., Pistorius S.R., Saeger H.D., Rothhammer V., Al-Taie O., Schackert H.K.
Hum. Mutat. 24:351-352(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 GLY-41 AND ASN-VAL-PHE-HIS-ILE-719 INS.
[92]"Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden."
Cederquist K., Emanuelsson M., Goeransson I., Holinski-Feder E., Mueller-Koch Y., Golovleva I., Groenberg H.
Int. J. Cancer 109:370-376(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 VAL-21; ARG-67; ASN-68 AND LYS-616 DEL.
[93]Erratum
Cederquist K., Emanuelsson M., Goransson I., Holinski-Feder E., Muller-Koch Y., Golovleva I., Gronberg H.
Int. J. Cancer 115:1011-1011(2005)
[94]"Germline epimutation of MLH1 in individuals with multiple cancers."
Suter C.M., Martin D.I.K., Ward R.L.
Nat. Genet. 36:497-501(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN HNPCC2 BY EPIGENETIC INHERITANCE.
[95]"The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer."
Lipkin S.M., Rozek L.S., Rennert G., Yang W., Chen P.-C., Hacia J., Hunt N., Shin B., Fodor S., Kokoris M., Greenson J.K., Fearon E., Lynch H., Collins F., Gruber S.B.
Nat. Genet. 36:694-699(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CRC HIS-132.
[96]"Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1."
Raevaara T.E., Korhonen M.K., Lohi H., Hampel H., Lynch E., Loennqvist K.E., Holinski-Feder E., Sutter C., McKinnon W., Duraisamy S., Gerdes A.-M., Peltomaeki P., Kohonen-Corish M., Mangold E., Macrae F., Greenblatt M., de la Chapelle A., Nystroem M.
Gastroenterology 129:537-549(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 LEU-28; 45-THR--PHE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; PRO-550; ASP-589; VAL-612 DEL; LYS-616 DEL; LEU-648; SER-648; LEU-654 AND PRO-659, VARIANTS SER-29; GLY-93; MET-213; GLN-443; ALA-618; CYS-646; GLN-659; THR-681 AND MET-716, CHARACTERIZATION OF VARIANTS HNPCC2 LEU-28; 45-THR--PHE-47 DELINS CYS-PHE; GLU-63; ARG-67; GLU-71 DEL; ARG-77; VAL-80; GLU-84; ARG-107; ARG-155; GLY-185; PRO-247; PRO-329; ILE-330 DEL; PRO-550; ASP-589; VAL-612 DEL; LYS-616 DEL; THR-618; LEU-648; SER-648; LEU-654 AND PRO-659, CHARACTERIZATION OF VARIANTS SER-29; GLY-93; MET-213; VAL-219; GLN-443; ALA-618; CYS-646; GLN-659; THR-681 AND MET-716.
[97]"Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study)."
Kurzawski G., Suchy J., Lener M., Klujszo-Grabowska E., Kladny J., Safranow K., Jakubowska K., Jakubowska A., Huzarski T., Byrski T., Debniak T., Cybulski C., Gronwald J., Oszurek O., Oszutowska D., Kowalska E., Gozdz S., Niepsuj S. expand/collapse author list , Slomski R., Plawski A., Lacka-Wojciechowska A., Rozmiarek A., Fiszer-Maliszewska L., Bebenek M., Sorokin D., Sasiadek M.M., Stembalska A., Grzebieniak Z., Kilar E., Stawicka M., Godlewski D., Richter P., Brozek I., Wysocka B., Limon J., Jawien A., Banaszkiewicz Z., Janiszewska H., Kowalczyk J., Czudowska D., Scott R.J., Lubinski J.
Clin. Genet. 69:40-47(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 LEU-28; LYS-35; ARG-67; VAL-111; MET-117; PRO-292; THR-441; LYS-618 DEL; PRO-623; ILE-657 DEL; THR-681; TRP-687 AND ARG-751.
[98]"Biallelic germline mutations of mismatch-repair genes: a possible cause for multiple pediatric malignancies."
Rotterdam initiative on gastrointestinal hereditary tumors
Poley J.-W., Wagner A., Hoogmans M.M.C.P., Menko F.H., Tops C., Kros J.M., Reddingius R.E., Meijers-Heijboer H., Kuipers E.J., Dinjens W.N.M.
Cancer 109:2349-2356(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MMRCS ASN-35.
[99]"Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays."
Takahashi M., Shimodaira H., Andreutti-Zaugg C., Iggo R., Kolodner R.D., Ishioka C.
Cancer Res. 67:4595-4604(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HNPCC2 LYS-102 AND GLN-474.
[100]"Inheritance of a cancer-associated MLH1 germ-line epimutation."
Hitchins M.P., Wong J.J.L., Suthers G., Suter C.M., Martin D.I.K., Hawkins N.J., Ward R.L.
N. Engl. J. Med. 356:697-705(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN HNPCC2 BY GERMLINE EPIMUTATION.
[101]"Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer."
Barnetson R.A., Cartwright N., van Vliet A., Haq N., Drew K., Farrington S., Williams N., Warner J., Campbell H., Porteous M.E., Dunlop M.G.
Hum. Mutat. 29:367-374(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CRC GLU-67 AND THR-681, VARIANTS ALA-22; GLY-93; SER-309; ASN-406; HIS-607; ALA-618; ARG-689; MET-716; TYR-718 AND ARG-751.
[102]"A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects."
Tournier I., Vezain M., Martins A., Charbonnier F., Baert-Desurmont S., Olschwang S., Wang Q., Buisine M.P., Soret J., Tazi J., Frebourg T., Tosi M.
Hum. Mutat. 29:1412-1424(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HNPCC2 ILE-330 DEL, VARIANTS HIS-41; ARG-67; ARG-77; SER-98; SER-101; ASP-101; LYS-116; MET-117; ASN-126; MET-213; SER-215; SER-216; PHE-260; CYS-265; HIS-265; ASP-320; ALA-326; ILE-330 DEL; TRP-474; GLN-474; ASP-539; PRO-549; THR-551; ARG-585; ARG-603; HIS-607; PRO-619; SER-640; LEU-640; VAL-655; SER-656; ARG-666; THR-681 AND ARG-689.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U07343 mRNA. Translation: AAC50285.1.
U07418 mRNA. Translation: AAA17374.1.
U40978 expand/collapse EMBL AC list , U40960, U40961, U40962, U40963, U40964, U40965, U40966, U40967, U40968, U40969, U40970, U40971, U40972, U40973, U40974, U40975, U40976, U40977 Genomic DNA. Translation: AAA82079.1.
U17857 expand/collapse EMBL AC list , U17839, U17840, U17841, U17842, U17843, U17844, U17845, U17846, U17847, U17848, U17849, U17851, U17852, U17853, U17854, U17855, U17856 Genomic DNA. Translation: AAA85687.1.
AY217549 Genomic DNA. Translation: AAO22994.1.
AK295359 mRNA. Translation: BAG58325.1.
AK298324 mRNA. Translation: BAG60576.1.
AK298583 mRNA. Translation: BAG60773.1.
AK316074 mRNA. Translation: BAH14445.1.
AK316264 mRNA. Translation: BAH14635.1.
AC006583 Genomic DNA. No translation available.
AC011816 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64483.1.
BC006850 mRNA. Translation: AAH06850.1.
PIRS43085.
RefSeqNP_000240.1. NM_000249.3.
NP_001161089.1. NM_001167617.1.
NP_001161090.1. NM_001167618.1.
NP_001161091.1. NM_001167619.1.
NP_001245200.1. NM_001258271.1.
NP_001245202.1. NM_001258273.1.
NP_001245203.1. NM_001258274.1.
XP_005265220.1. XM_005265163.1.
XP_005265221.1. XM_005265164.1.
UniGeneHs.195364.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3NA3X-ray2.50A1-347[»]
3RBNX-ray2.16A/B486-751[»]
ProteinModelPortalP40692.
SMRP40692. Positions 3-335, 487-751.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110438. 117 interactions.
DIPDIP-27601N.
IntActP40692. 95 interactions.
MINTMINT-257265.
STRING9606.ENSP00000231790.

PTM databases

PhosphoSiteP40692.

Polymorphism databases

DMDM730028.

Proteomic databases

PaxDbP40692.
PRIDEP40692.

Protocols and materials databases

DNASU4292.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000231790; ENSP00000231790; ENSG00000076242. [P40692-1]
ENST00000435176; ENSP00000402564; ENSG00000076242. [P40692-3]
ENST00000455445; ENSP00000398272; ENSG00000076242. [P40692-2]
ENST00000458205; ENSP00000402667; ENSG00000076242. [P40692-2]
ENST00000539477; ENSP00000443665; ENSG00000076242. [P40692-2]
GeneID4292.
KEGGhsa:4292.
UCSCuc003cgl.3. human. [P40692-1]
uc010hgk.3. human.

Organism-specific databases

CTD4292.
GeneCardsGC03P037034.
HGNCHGNC:7127. MLH1.
HPACAB013294.
HPA052707.
MIM120436. gene.
158320. phenotype.
276300. phenotype.
608089. phenotype.
609310. phenotype.
neXtProtNX_P40692.
Orphanet252202. Constitutional mismatch repair deficiency syndrome.
144. Hereditary nonpolyposis colon cancer.
587. Muir-Torre syndrome.
99817. Non-polyposis Turcot syndrome.
PharmGKBPA240.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0323.
HOGENOMHOG000176000.
HOVERGENHBG006374.
InParanoidP40692.
KOK08734.
OMAINHRCVE.
OrthoDBEOG7MSMNH.
PhylomeDBP40692.
TreeFamTF300493.

Enzyme and pathway databases

ReactomeREACT_111183. Meiosis.

Gene expression databases

ArrayExpressP40692.
BgeeP40692.
CleanExHS_MLH1.
GenevestigatorP40692.

Family and domain databases

Gene3D3.30.230.10. 1 hit.
3.30.565.10. 1 hit.
InterProIPR013507. DNA_mismatch_repair_C.
IPR014762. DNA_mismatch_repair_CS.
IPR002099. DNA_mismatch_repair_fam.
IPR011186. DNA_mismatch_repair_MLH1.
IPR003594. HATPase_ATP-bd.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view]
PANTHERPTHR10073. PTHR10073. 1 hit.
PTHR10073:SF11. PTHR10073:SF11. 1 hit.
PfamPF01119. DNA_mis_repair. 1 hit.
[Graphical view]
SMARTSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMSSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
TIGRFAMsTIGR00585. mutl. 1 hit.
PROSITEPS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMlh1. human.
EvolutionaryTraceP40692.
GeneWikiMLH1.
GenomeRNAi4292.
NextBio16893.
PMAP-CutDBP40692.
PROP40692.
SOURCESearch...

Entry information

Entry nameMLH1_HUMAN
AccessionPrimary (citable) accession number: P40692
Secondary accession number(s): B4DI13, B4DQ11, E9PCU2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 16, 2014
This is version 166 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM