P40692 (MLH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA mismatch repair protein Mlh1

Alternative name(s):
MutL protein homolog 1

Gene names

Name:	MLH1
Synonyms:	COCA2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	756 AA.
Sequence status	Complete.
Protein existence	Evidence 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.28 Ref.29 Ref.30 Ref.31 Ref.33 Ref.34 Ref.36 Ref.37 Ref.38 Ref.39 Ref.41 Ref.42 Ref.44 Ref.45 Ref.47 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60 Ref.61 Ref.62 Ref.63 Ref.65 Ref.68 Ref.70 Ref.71 Ref.72 Ref.73 Ref.75 Ref.76 Ref.77 Ref.78 Ref.79 Ref.80 Ref.81 Ref.82 Ref.84 Ref.86 Ref.87 Ref.88 Ref.90 Ref.91 Ref.93 Ref.95 Ref.96 Ref.98 Ref.99 Ref.101 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.27 Ref.97 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.66 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 process	Cell cycle DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Hereditary nonpolyposis colorectal cancer Tumor suppressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	double-strand break repair via nonhomologous end joining Inferred from electronic annotation. Source: Compara intrinsic apoptotic signaling pathway in response to DNA damage Inferred from electronic annotation. Source: Compara isotype switching Inferred from electronic annotation. Source: Compara male meiosis chromosome segregation Inferred from electronic annotation. Source: Compara meiotic metaphase I plate congression Inferred from electronic annotation. Source: Compara mismatch repair Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of mitotic recombination Inferred from electronic annotation. Source: Compara nuclear-transcribed mRNA poly(A) tail shortening Inferred from electronic annotation. Source: Compara oogenesis Inferred from electronic annotation. Source: Compara pachytene Inferred from electronic annotation. Source: Compara reciprocal meiotic recombination Inferred from Biological aspect of Ancestor. Source: RefGenome resolution of meiotic recombination intermediates Inferred from electronic annotation. Source: Compara somatic hypermutation of immunoglobulin genes Inferred from Biological aspect of Ancestor. Source: RefGenome spermatogenesis Inferred from electronic annotation. Source: Compara spindle midzone assembly involved in meiosis Inferred from electronic annotation. Source: Compara
Cellular_component	MutLalpha 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: Compara synaptonemal complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	ATP 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: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACTG1	P63261	7	EBI-744248,EBI-351292
ANXA2	P07355	7	EBI-744248,EBI-352622
CTSB	P07858	7	EBI-744248,EBI-715062
DES	P17661	7	EBI-744248,EBI-1055572
FSCN1	Q16658	7	EBI-744248,EBI-351076
NT5C3L	Q969T7	3	EBI-744248,EBI-2932564
PMS2	P54278	3	EBI-744248,EBI-1162561
SPTAN1	Q13813	7	EBI-744248,EBI-351450
TMSB4X	P62328	16	EBI-744248,EBI-712598
ZC3H11A	O75152	3	EBI-744248,EBI-748480

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 756

756

DNA mismatch repair protein Mlh1

PRO_0000178000

Regions

Region

410 – 650

241

Interaction with EXO1

Amino acid modifications

Modified residue

477

1

Phosphoserine Ref.22 Ref.23 Ref.26

Natural variations

Alternative sequence

1 – 241

241

Missing in isoform 2.

VSP_045201

Natural variant

18

1

R → C in HNPCC2. Ref.86

VAR_022663

Natural variant

19

1

I → F in HNPCC2; uncertain pathogenicity. Ref.81

VAR_043383

Natural variant

21

1

A → V in HNPCC2. Ref.91

VAR_043384

Natural variant

22

1

G → A. Ref.100
Corresponds to variant rs41295280 [ dbSNP | Ensembl ].

VAR_038023

Natural variant

25

1

I → F in HNPCC2. Ref.59

VAR_043385

Natural variant

28

1

P → L in HNPCC2. Ref.41 Ref.56 Ref.81 Ref.95 Ref.96

VAR_004433

Natural variant

29

1

A → S in HNPCC2; unknown pathological significance; has no effect on ex vivo splicing assay. Ref.82 Ref.95

VAR_043386

Natural variant

32

1

I → V. Ref.5
Corresponds to variant rs2020872 [ dbSNP | Ensembl ].

VAR_014876

Natural variant

35

1

M → K in HNPCC2; unknown pathological significance. Ref.96

VAR_043387

Natural variant

35

1

M → N in MMRCS; requires 2 nucleotide substitutions. Ref.73 Ref.97

VAR_043388

Natural variant

35

1

M → R in HNPCC2.

VAR_004434

Natural variant

37

1

E → ELNH Found in an endometrial cancer sample; somatic mutation.

VAR_004435

Natural variant

38

1

N → H in HNPCC2. Ref.73

VAR_043389

Natural variant

41

1

D → G in HNPCC2. Ref.90

VAR_043390

Natural variant

41

1

D → H Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054522

Natural variant

44

1

S → 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.44

VAR_004436

Natural variant

45 – 47

3

TSI → CF in HNPCC2.

VAR_043391

Natural variant

54

1

G → E in CRC; sporadic; somatic mutation. Ref.35

VAR_012902

Natural variant

62

1

Q → K in HNPCC2; reduced repair efficiency in a yeast mismatch repair assay. Ref.33

VAR_004437

Natural variant

63

1

D → E in HNPCC2. Ref.95

VAR_043392

Natural variant

64

1

N → S in HNPCC2. Ref.33

VAR_004438

Natural variant

67

1

G → E in CRC. Ref.100

VAR_038024

Natural variant

67

1

G → 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.39 Ref.52 Ref.53 Ref.82 Ref.91 Ref.95 Ref.96 Ref.101

VAR_004439

Natural variant

67

1

G → W in HNPCC2. Ref.54 Ref.57

VAR_012903

Natural variant

68

1

I → N in HNPCC2; the equivalent substitution in yeast causes loss of function in a mismatch repair assay. Ref.91

VAR_004440

Natural variant

69

1

R → K in HNPCC2; reduced repair efficiency in a mismatch repair assay. Ref.49

VAR_004441

Natural variant

71

1

Missing in HNPCC2. Ref.95

VAR_043393

Natural variant

77

1

C → R in HNPCC2 and CRC; sporadic; normal interaction with PMS2; loss of function in a mismatch repair assay. Ref.50 Ref.77 Ref.95 Ref.101

VAR_004442

Natural variant

77

1

C → Y in CRC; sporadic; early onset. Ref.43

VAR_012904

Natural variant

80

1

F → V in HNPCC2. Ref.68 Ref.95

VAR_012905

Natural variant

84

1

K → E in HNPCC2. Ref.56 Ref.95

VAR_012906

Natural variant

93

1

S → G Common polymorphism; normal interaction with PMS2; no functional alteration detected by an in vitro mismatch repair assay. Ref.51 Ref.77 Ref.95 Ref.100
Corresponds to variant rs41295282 [ dbSNP | Ensembl ].

VAR_004443

Natural variant

98

1

G → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054523

Natural variant

101

1

G → D in HNPCC2; has no effect on ex vivo splicing assay. Ref.86 Ref.101

VAR_022664

Natural variant

101

1

G → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054524

Natural variant

102

1

E → K in HNPCC2; uncertain pathogenicity. Ref.98

VAR_043394

Natural variant

106

1

S → R in gastric cancer; uncertain pathogenicity. Ref.65

VAR_043395

Natural variant

107

1

I → R in HNPCC2; normal interaction with PMS2; loss of function in a mismatch repair assay. Ref.77 Ref.95

VAR_004444

Natural variant

109

1

H → Q in gastric cancer; uncertain pathogenicity. Ref.65

VAR_043396

Natural variant

111

1

A → V in HNPCC2; uncertain pathogenicity. Ref.61 Ref.96

VAR_012907

Natural variant

116

1

T → K Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054525

Natural variant

117

1

T → 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.29 Ref.57 Ref.73 Ref.75 Ref.79 Ref.81 Ref.96 Ref.101

VAR_004445

Natural variant

117

1

T → R in HNPCC2; equivalent substitution in yeast causes loss of function in mismatch repair assay. Ref.53

VAR_004446

Natural variant

126

1

Y → N Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054526

Natural variant

128

1

A → P in HNPCC2. Ref.36

VAR_012908

Natural variant

132

1

D → H in CRC; sporadic; susceptibility to; ATPase function attenuated but not eliminated. Ref.94
Corresponds to variant rs28930073 [ dbSNP | Ensembl ].

VAR_022665

Natural variant

155

1

L → R in HNPCC2. Ref.95

VAR_043397

Natural variant

182

1

R → G in HNPCC2; incomplete. Ref.42 Ref.57

VAR_012909

Natural variant

182

1

R → K in HNPCC2. Ref.86

VAR_022666

Natural variant

185

1

V → G in HNPCC2; defective in a mismatch repair assay; has no effect on ex vivo splicing assay. Ref.75 Ref.95

VAR_004447

Natural variant

185

1

V → L in HNPCC2; unknown pathological significance. Ref.82

VAR_043398

Natural variant

193

1

S → P in HNPCC2. Ref.50

VAR_004448

Natural variant

213

1

V → M Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.5 Ref.62 Ref.76 Ref.95 Ref.101
Corresponds to variant rs2308317 [ dbSNP | Ensembl ].

VAR_012910

Natural variant

215

1

N → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054527

Natural variant

216

1

I → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054528

Natural variant

217

1

R → C in HNPCC2; unknown pathological significance; proficient in a mismatch repair assay. Ref.31 Ref.47 Ref.75 Ref.88
Corresponds to variant rs4986984 [ dbSNP | Ensembl ].

VAR_004449

Natural variant

217

1

R → G.

VAR_020469

Natural variant

219

1

I → V Common polymorphism; found in 37% of alleles. Ref.5 Ref.35 Ref.36 Ref.39 Ref.43 Ref.52 Ref.53 Ref.61 Ref.74 Ref.75 Ref.78 Ref.79 Ref.81 Ref.95
Corresponds to variant rs1799977 [ dbSNP | Ensembl ].

VAR_004450

Natural variant

226 – 295

70

Missing in HNPCC2.

VAR_004452

Natural variant

226

1

R → L in HNPCC2. Ref.29

VAR_004451

Natural variant

234

1

E → G in HNPCC2; uncertain pathogenicity. Ref.65

VAR_043399

Natural variant

244

1

G → D in HNPCC2; defective in a mismatch repair assay. Ref.36 Ref.75 Ref.82

VAR_012911

Natural variant

244

1

G → V in CRC; sporadic; somatic mutation; unknown pathological significance. Ref.35

VAR_012912

Natural variant

247

1

S → P in HNPCC2. Ref.79 Ref.95

VAR_043400

Natural variant

260

1

L → F Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054529

Natural variant

260

1

L → R in CRC. Ref.63

VAR_043401

Natural variant

262

1

Missing in HNPCC2. Ref.52

VAR_012913

Natural variant

264

1

H → Y in HNPCC2. Ref.60

VAR_043402

Natural variant

265

1

R → C Associated with HNPCC2; results in partial exon 10 skipping on ex vivo splicing assay. Ref.101

VAR_054530

Natural variant

265

1

R → H Rare polymorphism; associated with HNPCC2; slightly lower mismatch repair efficiency; results in partial exon 10 skipping on ex vivo splicing assay. Ref.34 Ref.55 Ref.75 Ref.101

VAR_012914

Natural variant

268

1

E → G in CRC. Ref.46

VAR_012915

Natural variant

282

1

A → G in HNPCC2. Ref.88

VAR_043403

Natural variant

292

1

L → P in HNPCC2; uncertain pathogenicity. Ref.81 Ref.96

VAR_043404

Natural variant

295

1

S → T in HNPCC2. Ref.42

VAR_012916

Natural variant

304

1

D → V in HNPCC2. Ref.63

VAR_043405

Natural variant

309

1

P → S. Ref.100

VAR_038025

Natural variant

320

1

E → D Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054531

Natural variant

321

1

S → I in HNPCC2; uncertain pathogenicity. Ref.65

VAR_043406

Natural variant

325 – 327

3

Missing in colorectal cancer.

VAR_043407

Natural variant

325

1

R → Q in CRC; sporadic; somatic mutation; unknown pathological significance. Ref.35

VAR_012917

Natural variant

326

1

V → A in HNPCC2; proficient in a mismatch repair assay. Ref.55 Ref.75 Ref.101

VAR_004453

Natural variant

329

1

H → P in HNPCC2. Ref.38 Ref.56 Ref.68 Ref.95

VAR_012918

Natural variant

330

1

Missing in HNPCC2; results in weak exon 11 skipping on ex vivo splicing assay. Ref.95 Ref.101

VAR_043408

Natural variant

338

1

N → S in HNPCC2. Ref.72

VAR_043409

Natural variant

379

1

Y → C in HNPCC2. Ref.86

VAR_022667

Natural variant

384

1

V → D Can be associated with HNPCC in some populations. Ref.32 Ref.48 Ref.61

VAR_004454

Natural variant

385

1

R → C in HNPCC2; unknown pathological significance. Ref.76

VAR_043410

Natural variant

385

1

R → P in HNPCC2; unknown pathological significance. Ref.55

VAR_043411

Natural variant

406

1

S → N. Ref.35 Ref.55 Ref.100
Corresponds to variant rs41294980 [ dbSNP | Ensembl ].

VAR_012919

Natural variant

441

1

A → T in HNPCC2. Ref.44 Ref.96

VAR_012920

Natural variant

443

1

K → Q. Ref.95
Corresponds to variant rs34213726 [ dbSNP | Ensembl ].

VAR_043412

Natural variant

472

1

R → I in CRC; uncertain pathogenicity. Ref.65

VAR_043413

Natural variant

474

1

R → Q in HNPCC2; has no effect on ex vivo splicing assay; uncertain pathogenicity. Ref.98 Ref.101

VAR_043414

Natural variant

474

1

R → W Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054532

Natural variant

485

1

D → E in HNPCC2. Ref.53

VAR_043415

Natural variant

485

1

D → H in HNPCC2; uncertain pathogenicity. Ref.65

VAR_043416

Natural variant

492

1

A → T in HNPCC2 and CRC; sporadic. Ref.30

VAR_004455

Natural variant

506

1

V → A in HNPCC2.

VAR_004456

Natural variant

539

1

A → D Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054533

Natural variant

542

1

Q → L in HNPCC2; type II; equivalent substitution in yeast causes loss of function in a mismatch repair assay. Ref.4 Ref.31 Ref.88

VAR_004457

Natural variant

542

1

Q → P in HNPCC2. Ref.88

VAR_043417

Natural variant

549

1

L → P in HNPCC2; has no effect on ex vivo splicing assay. Ref.31 Ref.88 Ref.101

VAR_012921

Natural variant

550

1

L → P in HNPCC2. Ref.95

VAR_043418

Natural variant

551

1

N → T in HNPCC2; has no effect on ex vivo splicing assay. Ref.42 Ref.52 Ref.101

VAR_012922

Natural variant

559

1

L → R in HNPCC2. Ref.86

VAR_022668

Natural variant

565

1

I → F in HNPCC2. Ref.52

VAR_012923

Natural variant

574

1

L → P in HNPCC2; type I; abrogates interaction with EXO1. Ref.4 Ref.12 Ref.31 Ref.88

VAR_004458

Natural variant

578

1

E → G in HNPCC2 and CRC. Ref.58

VAR_004459

Natural variant

582

1

L → V in HNPCC2; type II. Ref.4

VAR_004460

Natural variant

585

1

L → R Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054534

Natural variant

586

1

A → P in HNPCC2. Ref.84

VAR_015689

Natural variant

588

1

L → P in HNPCC2. Ref.61

VAR_012924

Natural variant

589

1

A → D in HNPCC2. Ref.95

VAR_043419

Natural variant

596

1

Missing in HNPCC2.

VAR_043420

Natural variant

601

1

D → G in CRC; uncertain pathogenicity. Ref.85

VAR_043421

Natural variant

603

1

P → R in HNPCC2; unknown pathological significance; has no effect on ex vivo splicing assay. Ref.68 Ref.72 Ref.101
Corresponds to variant rs35831931 [ dbSNP | Ensembl ].

VAR_012925

Natural variant

607

1

L → 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.62 Ref.66 Ref.76 Ref.100 Ref.101
Corresponds to variant rs41295284 [ dbSNP | Ensembl ].

VAR_012926

Natural variant

612

1

Missing in HNPCC2. Ref.95

VAR_043422

Natural variant

616

1

Missing in HNPCC2 and MMRCS; abrogates interaction with EXO1; has no effect on ex vivo splicing assay. Ref.12 Ref.27 Ref.28 Ref.30 Ref.33 Ref.34 Ref.57 Ref.86 Ref.91 Ref.95

VAR_004461

Natural variant

618

1

K → A Common polymorphism; requires 2 nucleotide substitutions. Ref.33 Ref.58 Ref.62 Ref.68 Ref.73 Ref.79 Ref.80 Ref.95 Ref.100
Corresponds to variant rs35502531 [ dbSNP | Ensembl ].

VAR_004462

Natural variant

618

1

K → R in colorectal cancer. Ref.83

VAR_043424

Natural variant

618

1

K → T in HNPCC2; type II. Ref.4 Ref.30 Ref.55 Ref.72 Ref.76 Ref.95

VAR_004463

Natural variant

618

1

Missing in HNPCC2. Ref.96

VAR_043423

Natural variant

619

1

A → P Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054535

Natural variant

622

1

L → H in HNPCC2. Ref.71

VAR_012927

Natural variant

623

1

A → P in HNPCC2; uncertain pathogenicity. Ref.96

VAR_043425

Natural variant

626 – 627

2

FS → ST in HNPCC2.

VAR_004464

Natural variant

631

1

D → A in HNPCC2; uncertain pathogenicity. Ref.65

VAR_043426

Natural variant

635

1

N → K in gastric cancer; uncertain pathogenicity. Ref.65

VAR_043427

Natural variant

636

1

L → P in HNPCC2. Ref.88

VAR_043428

Natural variant

640

1

P → L Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054536

Natural variant

640

1

P → S in HNPCC2; has no effect on ex vivo splicing assay. Ref.88 Ref.101

VAR_043429

Natural variant

646

1

Y → C in HNPCC2; unknown pathological significance. Ref.80 Ref.95
Corresponds to variant rs35045067 [ dbSNP | Ensembl ].

VAR_043430

Natural variant

648

1

P → L in HNPCC2. Ref.68 Ref.95

VAR_012928

Natural variant

648

1

P → S in HNPCC2; protein unstable but still functional in mismatch repair. Ref.76 Ref.87 Ref.95

VAR_022669

Natural variant

654

1

P → L in HNPCC2. Ref.95

VAR_043431

Natural variant

655

1

I → V Found in an endometrial cancer sample; also associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.74 Ref.101
Corresponds to variant rs55907433 [ dbSNP | Ensembl ].

VAR_043432

Natural variant

656

1

F → S Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054537

Natural variant

657

1

Missing in HNPCC2; uncertain pathogenicity. Ref.96

VAR_043433

Natural variant

659

1

R → L in HNPCC2. Ref.12 Ref.62

VAR_012929

Natural variant

659

1

R → 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.33 Ref.77 Ref.95

VAR_004465

Natural variant

659

1

R → Q. Ref.95

VAR_043434

Natural variant

662

1

T → P in HNPCC2; unknown pathological significance. Ref.68 Ref.78

VAR_012930

Natural variant

666

1

W → R Associated with HNPCC2; has no effect on ex vivo splicing assay. Ref.101

VAR_054538

Natural variant

681

1

A → T in HNPCC2; unknown pathological significance; equivalent substitution in yeast does not affect mismatch repair; abrogates interaction with EXO1. Ref.12 Ref.81 Ref.95 Ref.96 Ref.100 Ref.101

VAR_004466

Natural variant

687

1

R → W in HNPCC2; unknown pathological significance. Ref.71 Ref.81 Ref.96

VAR_012931

Natural variant

689

1

Q → R in HNPCC; unknown pathological significance. Ref.68 Ref.100 Ref.101

VAR_012932

Natural variant

716

1

V → M. Ref.52 Ref.55 Ref.68 Ref.79 Ref.95 Ref.100
Corresponds to variant rs35831931 [ dbSNP | Ensembl ].

VAR_012933

Natural variant

718

1

H → Y in HNPCC2; unknown pathological significance. Ref.59 Ref.72 Ref.100
Corresponds to variant rs2020873 [ dbSNP | Ensembl ].

VAR_004467

Natural variant

719

1

I → INVFHI in HNPCC2.

VAR_043435

Natural variant

724

1

L → M in HNPCC2. Ref.88

VAR_043436

Natural variant

729

1

L → V.
Corresponds to variant rs1800149 [ dbSNP | Ensembl ].

VAR_004468

Natural variant

749

1

L → P in colorectal cancer. Ref.83

VAR_043437

Natural variant

751

1

K → R in HNPCC2; unknown pathological significance. Ref.70 Ref.96 Ref.100

VAR_012934

Natural variant

755

1

R → W in HNPCC; incomplete. Ref.57

VAR_012935

Experimental info

Sequence conflict

708 – 711

4

Missing in AAA85687. Ref.4

Secondary structure

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756

Helix Strand Turn

Details...

Helix

13 – 24

12

Helix

28 – 41

14

Beta strand

45 – 52

8

Turn

53 – 56

4

Beta strand

57 – 63

7

Helix

70 – 74

5

Turn

75 – 77

3

Helix

103 – 109

7

Beta strand

110 – 118

9

Beta strand

123 – 131

9

Beta strand

134 – 137

4

Beta strand

140 – 142

3

Beta strand

146 – 154

9

Turn

155 – 158

4

Helix

160 – 164

5

Helix

169 – 186

18

Beta strand

191 – 196

6

Beta strand

203 – 205

3

Helix

212 – 220

9

Helix

222 – 225

4

Beta strand

228 – 235

8

Helix

236 – 238

3

Beta strand

240 – 247

8

Beta strand

253 – 255

3

Beta strand

257 – 262

6

Helix

272 – 281

10

Beta strand

291 – 297

7

Helix

324 – 334

11

Helix

504 – 516

13

Helix

519 – 526

8

Beta strand

529 – 543

15

Beta strand

546 – 551

6

Helix

552 – 566

15

Beta strand

572 – 581

10

Helix

582 – 590

9

Helix

593 – 595

3

Helix

604 – 626

23

Beta strand

634 – 641

8

Helix

650 – 652

3

Helix

653 – 662

10

Helix

669 – 684

16

Helix

688 – 690

3

Helix

712 – 718

7

Helix

720 – 724

5

Helix

732 – 735

4

Beta strand

737 – 745

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: C9231FC406C2CA20	FASTA	756	84,601
	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
	Isoform 2 [UniParc]. Checksum: DCD9320AB8E5ADF5	FASTA	515	58,375
	10 20 30 40 50 60 MNGYISNANY SVKKCIFLLF INHRLVESTS LRKAIETVYA AYLPKNTHPF LYLSLEISPQ 70 80 90 100 110 120 NVDVNVHPTK HEVHFLHEES ILERVQQHIE SKLLGSNSSR MYFTQTLLPG LAGPSGEMVK 130 140 150 160 170 180 STTSLTSSST SGSSDKVYAH QMVRTDSREQ KLDAFLQPLS KPLSSQPQAI VTEDKTDISS 190 200 210 220 230 240 GRARQQDEEM LELPAPAEVA AKNQSLEGDT TKGTSEMSEK RGPTSSNPRK RHREDSDVEM 250 260 270 280 290 300 VEDDSRKEMT AACTPRRRII NLTSVLSLQE EINEQGHEVL REMLHNHSFV GCVNPQWALA 310 320 330 340 350 360 QHQTKLYLLN TTKLSEELFY QILIYDFANF GVLRLSEPAP LFDLAMLALD SPESGWTEED 370 380 390 400 410 420 GPKEGLAEYI VEFLKKKAEM LADYFSLEID EEGNLIGLPL LIDNYVPPLE GLPIFILRLA 430 440 450 460 470 480 TEVNWDEEKE CFESLSKECA MFYSIRKQYI SEESTLSGQQ SEVPGSIPNS WKWTVEHIVY 490 500 510 KALRSHILPP KHFTEDGNIL QLANLPDLYK VFERC

References

	« Hide 'large scale' referencesShow '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. , 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] (ISOFORM 2). 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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[27]	"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.
[28]	"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.
[29]	"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.
[30]	"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.
[31]	"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.
[32]	"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.
[33]	"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.
[34]	"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.
[35]	"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.
[36]	"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.
[37]	"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.
[38]	"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.
[39]	"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.
[40]	"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.
[41]	"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.
[42]	"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.
[43]	"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.
[44]	"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.
[45]	"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.
[46]	"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.
[47]	"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.
[48]	"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.
[49]	"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.
[50]	"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.
[51]	"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.
[52]	"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.
[53]	"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.
[54]	"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.
[55]	"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.
[56]	"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.
[57]	"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.
[58]	"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.
[59]	"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.
[60]	"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.
[61]	"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.
[62]	"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.
[63]	"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.
[64]	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)
[65]	"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.
[66]	"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.
[67]	"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.
[68]	"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.
[69]	"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.
[70]	"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.
[71]	"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.
[72]	"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.
[73]	"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.
[74]	"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.
[75]	"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.
[76]	"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.
[77]	"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.
[78]	"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.
[79]	"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.
[80]	"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.
[81]	"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. , 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.
[82]	"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. , 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.
[83]	"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.
[84]	"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.
[85]	"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.
[86]	"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.
[87]	"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.
[88]	"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.
[89]	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)
[90]	"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.
[91]	"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.
[92]	Erratum Cederquist K., Emanuelsson M., Goransson I., Holinski-Feder E., Muller-Koch Y., Golovleva I., Gronberg H. Int. J. Cancer 115:1011-1011(2005)
[93]	"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.
[94]	"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.
[95]	"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.
[96]	"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. , 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.
[97]	"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.
[98]	"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.
[99]	"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.
[100]	"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.
[101]	"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.

Web resources

Hereditary non-polyposis colorectal cancer db

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U07343 mRNA. Translation: AAC50285.1.
U07418 mRNA. Translation: AAA17374.1.
U40978 , U40960, U40961, U40962, U40963, U40964, U40965, U40966, U40967, U40968, U40969, U40970, U40971, U40972, U40973, U40974, U40975, U40976, U40977 Genomic DNA. Translation: AAA82079.1.
U17857 , 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.
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.

IPI

IPI00029754.
IPI00742734.

PIR

S43085.

RefSeq

NP_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.

UniGene

Hs.195364.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3NA3	X-ray	2.50	A	1-347	[»]
3RBN	X-ray	2.16	A/B	486-751	[»]

ProteinModelPortal

P40692.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27601N.

IntAct

P40692. 89 interactions.

MINT

MINT-257265.

STRING

9606.ENSP00000231790.

PTM databases

PhosphoSite

P40692.

Polymorphism databases

DMDM

730028.

Proteomic databases

PaxDb

P40692.

PRIDE

P40692.

Protocols and materials databases

DNASU

4292.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000231790; ENSP00000231790; ENSG00000076242.
ENST00000455445; ENSP00000398272; ENSG00000076242.
ENST00000458205; ENSP00000402667; ENSG00000076242.
ENST00000539477; ENSP00000443665; ENSG00000076242.

GeneID

4292.

KEGG

hsa:4292.

UCSC

uc003cgl.3. human.

Organism-specific databases

CTD

4292.

GeneCards

GC03P037034.

HGNC

HGNC:7127. MLH1.

HPA

CAB013294.

MIM

120436. gene.
158320. phenotype.
276300. phenotype.
608089. phenotype.
609310. phenotype.

neXtProt

NX_P40692.

Orphanet

144. Hereditary nonpolyposis colon cancer.
587. Muir-Torre syndrome.

PharmGKB

PA240.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0323.

HOGENOM

HOG000176000.

HOVERGEN

HBG006374.

InParanoid

P40692.

KO

K08734.

OMA

SIQVVVK.

OrthoDB

EOG43N7C7.

PhylomeDB

P40692.

Enzyme and pathway databases

Reactome

REACT_111183. Meiosis.

Gene expression databases

ArrayExpress

P40692.

Bgee

P40692.

CleanEx

HS_MLH1.

Genevestigator

P40692.

GermOnline

ENSG00000076242. Homo sapiens.

Family and domain databases

Gene3D

3.30.230.10. 1 hit.
3.30.565.10. 1 hit.

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.
[Graphical view]

PANTHER

PTHR10073. PTHR10073. 1 hit.
PTHR10073:SF11. PTHR10073:SF11. 1 hit.

Pfam

PF01119. DNA_mis_repair. 1 hit.
[Graphical view]

SMART

SM00387. HATPase_c. 1 hit.
[Graphical view]

SUPFAM

SSF55874. ATP_bd_ATPase. 1 hit.
SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit.

TIGRFAMs

TIGR00585. mutl. 1 hit.

PROSITE

PS00058. DNA_MISMATCH_REPAIR_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

Mlh1. human.

EvolutionaryTrace

P40692.

GenomeRNAi

4292.

NextBio

16893.

PMAP-CutDB

P40692.

SOURCE

Search...

Entry information

Entry name

MLH1_HUMAN

Accession

Primary (citable) accession number: P40692
Secondary accession number(s): B4DI13

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 155 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.