P43246 (MSH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA mismatch repair protein Msh2
Short name=hMSH2

Alternative name(s):
MutS protein homolog 2

Gene names

Name:

MSH2

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	934 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis. Ref.16 Ref.17 Ref.18 Ref.20 Ref.23 Ref.29 Ref.32
Subunit structure	Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta). Both heterodimer form a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. 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 ATR. Interacts with SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a subunit of different structure-specific endonucleases. Interacts with SMARCAD1. Ref.14 Ref.15 Ref.22 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.36 Ref.37
Subcellular location	Nucleus Potential.
Tissue specificity	Ubiquitously expressed. Ref.22
Post-translational modification	Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway. Ref.30
Involvement in disease	Hereditary non-polyposis colorectal cancer 1 (HNPCC1) [MIM:120435]: 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.3 Ref.19 Ref.41 Ref.44 Ref.46 Ref.47 Ref.48 Ref.49 Ref.52 Ref.53 Ref.54 Ref.56 Ref.59 Ref.61 Ref.62 Ref.63 Ref.64 Ref.66 Ref.67 Ref.69 Ref.70 Ref.72 Ref.73 Ref.74 Ref.77 Ref.78 Ref.79 Ref.80 Ref.81 Ref.83 Ref.84 Ref.85 Ref.87 Ref.88 Ref.89 Ref.90 Ref.91 Ref.92 Ref.93 Ref.94 Ref.95 Ref.96 Ref.97 Ref.98 Ref.99 Ref.101 Ref.102 Ref.103 Ref.104 Ref.105 Ref.107 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.4 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.
Sequence similarities	Belongs to the DNA mismatch repair MutS family.
Sequence caution	The sequence AAC27930.1 differs from that shown. Reason: Frameshift at position 417. The frameshift is caused by a single nucleotide deletion which is found in a HNPCC kindred.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Hereditary nonpolyposis colorectal cancer Tumor suppressor
Ligand	ATP-binding DNA-binding Nucleotide-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL cell cycle arrest Inferred from electronic annotation. Source: Compara determination of adult lifespan Inferred from electronic annotation. Source: Compara double-strand break repair Inferred from Biological aspect of Ancestor. Source: RefGenome germ cell development Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara intra-S DNA damage checkpoint Inferred from Biological aspect of Ancestor. Source: RefGenome intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Inferred from Biological aspect of Ancestor. Source: RefGenome isotype switching Inferred from sequence or structural similarity. Source: BHF-UCL maintenance of DNA repeat elements Inferred from mutant phenotype PubMed 16388310. Source: HGNC male gonad development Inferred from sequence or structural similarity. Source: BHF-UCL meiotic gene conversion Inferred from Biological aspect of Ancestor. Source: RefGenome meiotic mismatch repair Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of neuron apoptotic process Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of reciprocal meiotic recombination Inferred from Biological aspect of Ancestor. Source: RefGenome oxidative phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of helicase activity Inferred from direct assay PubMed 17715146. Source: BHF-UCL postreplication repair Inferred from direct assay Ref.12. Source: UniProtKB response to UV-B Inferred from sequence or structural similarity. Source: BHF-UCL response to X-ray Inferred from sequence or structural similarity. Source: BHF-UCL somatic hypermutation of immunoglobulin genes Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	MutSalpha complex Inferred from direct assay Ref.14. Source: HGNC MutSbeta complex Inferred from direct assay Ref.14. Source: HGNC nuclear chromosome Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA-dependent ATPase activity Inferred from Biological aspect of Ancestor. Source: RefGenome Y-form DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome centromeric DNA binding Inferred from electronic annotation. Source: Compara damaged DNA binding Inferred from electronic annotation. Source: Compara double-strand/single-strand DNA junction binding Inferred from Biological aspect of Ancestor. Source: RefGenome guanine/thymine mispair binding Inferred from mutant phenotype PubMed 16713580. Source: MGI loop DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome protein homodimerization activity Inferred from direct assay Ref.14. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EXO1	P39875	2	EBI-355888,EBI-6738	From a different organism.
MSH3	P20585	4	EBI-355888,EBI-1164205
MSH6	P52701	4	EBI-355888,EBI-395529
SLX4	Q8IY92	5	EBI-355888,EBI-2370740

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P43246-1)

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: P43246-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 934

934

DNA mismatch repair protein Msh2

PRO_0000115183

Regions

Nucleotide binding

669 – 676

8

ATP Potential

Region

601 – 671

71

Interaction with EXO1

Amino acid modifications

Modified residue

555

1

N6-acetyllysine Ref.38

Natural variations

Alternative sequence

1 – 66

66

Missing in isoform 2.

VSP_045536

Natural variant

2

1

A → T in HNPCC1. Ref.96

VAR_054511

Natural variant

8

1

T → M Could be associated with increased colorectal cancer susceptibility. Ref.9 Ref.64 Ref.86
Corresponds to variant rs17217716 [ dbSNP | Ensembl ].

VAR_013171

Natural variant

13

1

S → I in colorectal cancer. Ref.82

VAR_043736

Natural variant

17

1

V → F in gastric cancer; uncertain pathogenicity; cryptic acceptor splice site suppressed on ex vivo splicing assay. Ref.69

VAR_043737

Natural variant

33

1

T → P in HNPCC1; shows slightly reduced mismatch binding or release efficiency. Ref.97 Ref.101

VAR_043738

Natural variant

40

1

G → S in CRC. Ref.86

VAR_043739

Natural variant

43

1

Y → C. Ref.9
Corresponds to variant rs17217723 [ dbSNP | Ensembl ].

VAR_019233

Natural variant

44

1

T → M in HNPCC1; repair proficient. Ref.77 Ref.105

VAR_043740

Natural variant

45

1

A → V in HNPCC1; repair proficient. Ref.77 Ref.105

VAR_043741

Natural variant

46

1

H → Q in HNPCC1. Ref.46 Ref.100
Corresponds to variant rs33946261 [ dbSNP | Ensembl ].

VAR_004470

Natural variant

92

1

Missing in HNPCC1; uncertain pathogenicity; has no effect on ex vivo splicing assay. Ref.80 Ref.96 Ref.102

VAR_043742

Natural variant

93

1

L → F in HNPCC1. Ref.92

VAR_043743

Natural variant

96

1

R → H. Ref.5

VAR_004471

Natural variant

98

1

Y → C in HNPCC1; uncertain pathogenicity. Ref.69

VAR_043744

Natural variant

102

1

V → I in HNPCC1. Ref.78

VAR_043745

Natural variant

106

1

R → K. Ref.100
Corresponds to variant rs41295286 [ dbSNP | Ensembl ].

VAR_038026

Natural variant

110

1

K → T in HNPCC1; somatic mutation. Ref.49

VAR_043746

Natural variant

127

1

N → S in HNPCC1; shows significantly decreased repair efficiency when associated with variant Pro-328; presumed to enhance cancer risk considerably when associated with Pro-328; this concomitant defect with another variant could explain its recurrent occurrence in CRC patients. Ref.9 Ref.83 Ref.101 Ref.106
Corresponds to variant rs17217772 [ dbSNP | Ensembl ].

VAR_019234

Natural variant

139

1

N → S in HNPCC1.

VAR_004472

Natural variant

145

1

I → M in HNPCC1; mismatch repair proficient. Ref.96 Ref.106

VAR_004473

Natural variant

161

1

V → D in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. Ref.70 Ref.97 Ref.101

VAR_012936

Natural variant

162

1

G → A in HNPCC1. Ref.98

VAR_054512

Natural variant

162

1

G → R in HNPCC1; shows a decreased expression level of the MutS alpha complex and is associated with an abnormal subcellular localization pattern; affects protein stability; associated with an absence of the protein in tumors. Ref.95 Ref.97 Ref.101 Ref.103

VAR_043747

Natural variant

163

1

V → D in HNPCC1. Ref.78

VAR_043748

Natural variant

163

1

V → G in HNPCC1. Ref.85

VAR_022670

Natural variant

164

1

G → R in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. Ref.97 Ref.101

VAR_043749

Natural variant

165

1

Y → D Associated with HNPCC1; unknown pathological significance; repair deficient. Ref.105

VAR_067284

Natural variant

167

1

D → H in HNPCC1; does not show a decreased expression level of the MutS alpha complex and is not associated with an abnormal subcellular localization pattern; shows reduced mismatch binding; repair proficient. Ref.44 Ref.74 Ref.79 Ref.103 Ref.104 Ref.105

VAR_004474

Natural variant

169

1

I → V in HNPCC1; unknown pathological significance. Ref.86 Ref.93

VAR_043750

Natural variant

173

1

L → P in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. Ref.97 Ref.101

VAR_043751

Natural variant

175

1

L → P in HNPCC1. Ref.84

VAR_043752

Natural variant

177

1

E → H Associated with HNPCC1; requires 2 nucleotide substitutions; unknown pathological significance; repair proficient. Ref.105

VAR_067285

Natural variant

187

1

L → P in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. Ref.97 Ref.101

VAR_043753

Natural variant

198

1

E → G in HNPCC1.

VAR_054513

Natural variant

199

1

C → R in glioma; also associated with HNPCC1; has no effect on ex vivo splicing assay. Ref.55 Ref.102

VAR_012937

Natural variant

203

1

G → R in CRC; uncertain pathogenicity; somatic mutation. Ref.86

VAR_043754

Natural variant

205

1

E → Q Shows no defects; mismatch repair proficient. Ref.106

VAR_068705

Natural variant

216

1

I → V in HNPCC1; uncertain pathological significance; shows slightly reduced mismatch binding or release efficiency. Ref.70

VAR_012938

Natural variant

246

1

K → Q in HNPCC1; uncertain pathogenicity. Ref.61

VAR_043755

Natural variant

265 – 314

50

Missing in HNPCC1.

VAR_004475

Natural variant

272

1

A → V Associated with HNPCC1; unknown pathological significance; shows slightly reduced mismatch binding or release efficiency; results in partial exon 5 skipping on ex vivo splicing assay; repair proficient. Ref.97 Ref.101 Ref.102 Ref.105
Corresponds to variant rs34136999 [ dbSNP | Ensembl ].

VAR_043756

Natural variant

283

1

D → Y in HNPCC1. Ref.94

VAR_043757

Natural variant

305

1

A → T in HNPCC1; repair proficient. Ref.47 Ref.105

VAR_004476

Natural variant

322

1

G → D Common polymorphism; may be associated with increased colorectal cancer susceptibility; the equivalent substitution in yeast reduces the mismatch repair efficiency in vitro; shows significantly decreased repair efficiency when associated with variant Glu-487. Ref.9 Ref.43 Ref.51 Ref.53 Ref.57 Ref.60 Ref.61 Ref.65 Ref.67 Ref.71 Ref.76 Ref.78 Ref.80 Ref.82 Ref.96 Ref.100 Ref.101 Ref.106
Corresponds to variant rs4987188 [ dbSNP | Ensembl ].

VAR_004477

Natural variant

323

1

S → C in HNPCC1; unknown pathological significance. Ref.48

VAR_012939

Natural variant

323

1

S → Y in HNPCC1; unknown pathological significance. Ref.69

VAR_043758

Natural variant

328

1

A → P Shows significantly decreased repair efficiency when associated with variant Ser-127; presumed to enhance cancer risk considerably when associated with variant Ser-127. Ref.106

VAR_068706

Natural variant

331

1

N → D Associated with HNPCC1; has no effect on ex vivo splicing assay. Ref.102

VAR_054514

Natural variant

333

1

C → Y in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. Ref.97 Ref.101

VAR_043759

Natural variant

335

1

T → I in HNPCC1; unknown pathological significance. Ref.69

VAR_043760

Natural variant

336

1

P → S in HNPCC1. Ref.59

VAR_043761

Natural variant

342

1

V → I in colorectal cancer. Ref.82

VAR_043762

Natural variant

349

1

P → L in HNPCC1. Ref.91

VAR_043763

Natural variant

359

1

R → S in HNPCC1; shows a decreased expression level of the MutS alpha comp lex and is associated with an abnormal subcellular localization pattern. Ref.79 Ref.103

VAR_043764

Natural variant

367

1

V → I Shows no defects; mismatch repair proficient. Ref.106

VAR_068707

Natural variant

385

1

P → L Associated with HNPCC1; unknown pathological significance; repair proficient. Ref.105

VAR_067286

Natural variant

390

1

L → F in HNPCC1; unknown pathological significance; the equivalent substitution in yeast partially affects mismatch repair in vitro; repair proficient. Ref.9 Ref.42 Ref.58 Ref.60 Ref.62 Ref.86 Ref.93 Ref.96 Ref.105
Corresponds to variant rs17224367 [ dbSNP | Ensembl ].

VAR_004478

Natural variant

393

1

K → M in HNPCC1. Ref.74

VAR_043765

Natural variant

419

1

Q → K in CRC; uncertain pathogenicity; the equivalent substitution in yeast partially affects mismatch repair in vitro. Ref.42 Ref.60 Ref.86 Ref.93

VAR_012940

Natural variant

440

1

Missing in HNPCC1. Ref.89

VAR_043766

Natural variant

470

1

V → E Associated with HNPCC1; has no effect on ex vivo splicing assay. Ref.102

VAR_054515

Natural variant

487

1

D → E Mismatch repair deficient; shows significantly decreased repair efficiency when associated with variant Asp-322. Ref.106

VAR_068708

Natural variant

492

1

M → V in HNPCC1.

VAR_043767

Natural variant

506

1

D → Y in CRC; sporadic; early onset; the equivalent substitution in yeast partially affects mismatch repair in vitro. Ref.45 Ref.56 Ref.60 Ref.89

VAR_012941

Natural variant

519

1

F → L Associated with HNPCC1; unknown pathological significance; repair proficient. Ref.105

VAR_067287

Natural variant

524

1

R → P in HNPCC1; defective in mismatch repair activity. Ref.19 Ref.60 Ref.74

VAR_004479

Natural variant

552

1

T → P in HNPCC1. Ref.81

VAR_043768

Natural variant

554

1

S → R in HNPCC1; uncertain pathological significance. Ref.70

VAR_012942

Natural variant

562

1

E → V in HNPCC1. Ref.52

VAR_004480

Natural variant

564

1

T → A in HNPCC1; uncertain pathogenicity. Ref.78 Ref.93
Corresponds to variant rs55778204 [ dbSNP | Ensembl ].

VAR_043769

Natural variant

583

1

N → S in HNPCC1. Ref.81

VAR_043770

Natural variant

596

1

N → S in HNPCC1; uncertain pathological significance. Ref.50 Ref.61 Ref.100
Corresponds to variant rs41295288 [ dbSNP | Ensembl ].

VAR_012943

Natural variant

596

1

Missing in HNPCC1; has no effect on ex vivo splicing assay; repair deficient. Ref.41 Ref.44 Ref.47 Ref.59 Ref.74 Ref.77 Ref.91 Ref.102 Ref.105

VAR_004481

Natural variant

600

1

A → V in HNPCC1. Ref.73

VAR_043771

Natural variant

603

1

D → N in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. Ref.67 Ref.97 Ref.101

VAR_043772

Natural variant

610

1

H → N Associated with HNPCC1; has no effect on ex vivo splicing assay. Ref.102

VAR_054516

Natural variant

619

1

Y → C in CRC. Ref.86

VAR_043773

Natural variant

622

1

P → L in HNPCC1; the equivalent substitution in yeast causes loss of function in a mismatch repair assay; confers multiple biochemical defects. Ref.3 Ref.60 Ref.71 Ref.74 Ref.104
Corresponds to variant rs28929483 [ dbSNP | Ensembl ].

VAR_004482

Natural variant

629

1

Q → R in HNPCC1; uncertain pathogenicity. Ref.69 Ref.86 Ref.89 Ref.90 Ref.93

VAR_043774

Natural variant

636

1

A → P in HNPCC1; partial functional loss; mainly causes defects in mismatch binding or release efficiency. Ref.63 Ref.81 Ref.97 Ref.101

VAR_012944

Natural variant

638

1

R → G Associated with HNPCC1; has no effect on ex vivo splicing assay. Ref.102

VAR_054517

Natural variant

639

1

H → R in HNPCC1; shows reduced mismatch binding; repair proficient. Ref.49 Ref.104 Ref.105

VAR_043775

Natural variant

639

1

H → Y in HNPCC1; the equivalent substitution in yeast does not affect mismatch repair efficiency in vitro. Ref.3 Ref.71
Corresponds to variant rs28929484 [ dbSNP | Ensembl ].

VAR_004483

Natural variant

641

1

C → G. Ref.54

VAR_004484

Natural variant

645

1

Q → E Associated with HNPCC1; has no effect on ex vivo splicing assay. Ref.102

VAR_054518

Natural variant

647

1

E → K in HNPCC1. Ref.49

VAR_043776

Natural variant

656

1

Y → H in HNPCC1; somatic mutation. Ref.49

VAR_043777

Natural variant

660

1

D → G in HNPCC1. Ref.85

VAR_022671

Natural variant

669

1

G → R in HNPCC1. Ref.107

VAR_067761

Natural variant

670

1

P → L. Ref.100
Corresponds to variant rs41294982 [ dbSNP | Ensembl ].

VAR_038027

Natural variant

671

1

N → Y in HNPCC1; uncertain pathogenicity. Ref.88 Ref.102

VAR_043778

Natural variant

674

1

G → R in HNPCC1; confers resistance to ATP-dependent mismatch release; repair deficient. Ref.99 Ref.104 Ref.105

VAR_067288

Natural variant

674

1

G → S in HNPCC1; somatic mutation. Ref.74

VAR_004485

Natural variant

675

1

K → A Associated with HNPCC1; requires 2 nucleotide substitutions; unknown pathological significance; repair deficient. Ref.105

VAR_067289

Natural variant

679

1

I → T in HNPCC1; somatic mutation. Ref.49

VAR_043779

Natural variant

688

1

M → I in HNPCC1. Ref.56 Ref.64 Ref.89

VAR_012945

Natural variant

692

1

G → R in HNPCC1. Ref.66

VAR_009250

Natural variant

696

1

P → L Associated with HNPCC1; has no effect on ex vivo splicing assay. Ref.102

VAR_054519

Natural variant

697

1

C → F in HNPCC1; the equivalent substitution in yeast causes loss of function in a mismatch repair assay; mainly causes defects in mismatch binding or release efficiency; confers multiple biochemical defects; repair deficient. Ref.53 Ref.60 Ref.97 Ref.101 Ref.104 Ref.105

VAR_004486

Natural variant

697

1

C → R in HNPCC1; has no effect on ex vivo splicing assay. Ref.66 Ref.102

VAR_009251

Natural variant

714

1

A → V in HNPCC1; uncertain pathogenicity. Ref.69

VAR_043780

Natural variant

723

1

S → F in HNPCC1; has no effect on ex vivo splicing assay; repair deficient. Ref.73 Ref.102 Ref.105

VAR_043781

Natural variant

729

1

M → V in HNPCC1; somatic mutation. Ref.49

VAR_043782

Natural variant

732

1

T → I in HNPCC1; somatic mutation. Ref.49

VAR_043783

Natural variant

745 – 746

2

Missing in HNPCC1; mainly causes defects in mismatch binding or release efficiency.

VAR_043784

Natural variant

748

1

D → Y Associated with HNPCC1; has no effect on ex vivo splicing assay. Ref.102

VAR_054520

Natural variant

749

1

E → K in HNPCC1; mainly causes defects in mismatch binding or release efficiency; the mutant protein is well expressed in tumors. Ref.97 Ref.101

VAR_043785

Natural variant

759

1

G → E Associated with HNPCC1; unknown pathological significance; repair deficient. Ref.105

VAR_067290

Natural variant

770

1

I → V. Ref.54

VAR_004487

Natural variant

779

1

M → I. Ref.100
Corresponds to variant rs41295292 [ dbSNP | Ensembl ].

VAR_038028

Natural variant

805

1

L → V Associated with HNPCC1; unknown pathological significance; repair proficient. Ref.105

VAR_067291

Natural variant

807

1

T → S. Ref.100
Corresponds to variant rs41295294 [ dbSNP | Ensembl ].

VAR_038029

Natural variant

813

1

M → V in HNPCC1. Ref.72

VAR_043786

Natural variant

824

1

Q → E in gastric cancer; uncertain pathogenicity. Ref.69

VAR_043787

Natural variant

834

1

A → T in HNPCC1; shows no functional defects in gel shift assay; is nevertheless repair deficient. Ref.47 Ref.61 Ref.97 Ref.101 Ref.104

VAR_004488

Natural variant

835

1

N → H. Ref.100
Corresponds to variant rs41295296 [ dbSNP | Ensembl ].

VAR_038030

Natural variant

839

1

H → Q Associated with HNPCC1; has no effect on ex vivo splicing assay. Ref.102

VAR_054521

Natural variant

839

1

H → R in HNPCC1. Ref.90

VAR_043788

Natural variant

843

1

C → G Associated with HNPCC1; unknown pathological significance; repair proficient. Ref.105

VAR_067292

Natural variant

845

1

K → E in HNPCC1. Ref.64

VAR_013172

Natural variant

853

1

E → A in HNPCC1; uncertain pathogenicity. Ref.80 Ref.96

VAR_043789

Natural variant

860

1

S → L Associated with HNPCC1; unknown pathological significance; repair proficient. Ref.105

VAR_067293

Natural variant

868

1

P → A in gastric cancer; uncertain pathogenicity. Ref.69

VAR_043790

Natural variant

870

1

A → G in gastric cancer; uncertain pathogenicity. Ref.69

VAR_043791

Natural variant

873

1

C → G in gastric cancer; uncertain pathogenicity. Ref.69

VAR_043792

Natural variant

886

1

E → G in HNPCC1; repair proficient. Ref.77 Ref.105

VAR_043793

Natural variant

905

1

T → R in HNPCC1; uncertain pathological significance. Ref.74

VAR_004489

Natural variant

909

1

K → I Found in a colorectal cancer sample; mismatch repair proficient. Ref.106

VAR_068709

Natural variant

911

1

L → R. Ref.100
Corresponds to variant rs41295182 [ dbSNP | Ensembl ].

VAR_038031

Natural variant

923

1

V → E in HNPCC1; uncertain pathological significance. Ref.77 Ref.97 Ref.101

VAR_043794

Natural variant

931

1

K → T in HNPCC1. Ref.87

VAR_043795

Experimental info

Mutagenesis

674

1

G → A: Mainly causes defects in mismatch binding or release efficiency. Ref.101

Mutagenesis

675

1

K → R: No effect on mismatch binding, complete loss of DNA repair function when associated with MSH6 mutant R-1140. Ref.18

Sequence conflict

784

1

F → I in BX649122. Ref.7

Sequence conflict

836

1

F → S in BX649122. Ref.7

Secondary structure

1

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934

Helix Strand Turn

Details...

Helix

14 – 24

11

Beta strand

33 – 38

6

Beta strand

40 – 46

7

Helix

48 – 56

9

Beta strand

59 – 61

3

Beta strand

65 – 71

7

Beta strand

75 – 81

7

Helix

82 – 94

13

Beta strand

99 – 105

7

Beta strand

117 – 124

8

Helix

129 – 131

3

Helix

132 – 135

4

Beta strand

147 – 152

6

Beta strand

155 – 158

4

Beta strand

160 – 167

8

Turn

168 – 171

4

Beta strand

172 – 179

8

Helix

185 – 194

10

Beta strand

197 – 204

8

Helix

208 – 220

13

Beta strand

223 – 227

5

Helix

229 – 232

4

Helix

237 – 244

8

Turn

252 – 254

3

Helix

255 – 257

3

Helix

259 – 262

4

Helix

264 – 277

14

Helix

279 – 281

3

Helix

283 – 285

3

Beta strand

289 – 293

5

Helix

296 – 298

3

Helix

304 – 309

6

Helix

326 – 330

5

Helix

336 – 347

12

Helix

353 – 367

15

Helix

370 – 377

8

Turn

378 – 380

3

Helix

381 – 383

3

Helix

387 – 395

9

Helix

401 – 411

11

Helix

414 – 423

10

Beta strand

424 – 426

3

Beta strand

427 – 429

3

Helix

432 – 435

4

Helix

437 – 455

19

Helix

462 – 464

3

Turn

472 – 474

3

Helix

476 – 502

27

Turn

507 – 509

3

Beta strand

512 – 515

4

Turn

517 – 519

3

Beta strand

521 – 525

5

Helix

527 – 530

4

Turn

531 – 535

5

Beta strand

540 – 544

5

Beta strand

549 – 552

4

Helix

556 – 563

8

Turn

564 – 567

4

Helix

568 – 585

18

Helix

586 – 588

3

Helix

589 – 613

25

Beta strand

615 – 617

3

Beta strand

623 – 625

3

Beta strand

631 – 637

7

Turn

640 – 644

5

Beta strand

653 – 658

6

Turn

659 – 661

3

Beta strand

664 – 668

5

Helix

675 – 691

17

Beta strand

695 – 703

9

Beta strand

706 – 711

6

Helix

724 – 738

15

Beta strand

744 – 749

6

Helix

756 – 772

17

Beta strand

777 – 783

7

Helix

785 – 792

8

Beta strand

797 – 807

11

Beta strand

810 – 820

11

Helix

827 – 833

7

Helix

838 – 850

13

Turn

851 – 855

5

Helix

875 – 892

18

Helix

896 – 898

3

Helix

901 – 917

17

Helix

921 – 928

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 664A058C78242E05	FASTA	934	104,743
	10 20 30 40 50 60 MAVQPKETLQ LESAAEVGFV RFFQGMPEKP TTTVRLFDRG DFYTAHGEDA LLAAREVFKT 70 80 90 100 110 120 QGVIKYMGPA GAKNLQSVVL SKMNFESFVK DLLLVRQYRV EVYKNRAGNK ASKENDWYLA 130 140 150 160 170 180 YKASPGNLSQ FEDILFGNND MSASIGVVGV KMSAVDGQRQ VGVGYVDSIQ RKLGLCEFPD 190 200 210 220 230 240 NDQFSNLEAL LIQIGPKECV LPGGETAGDM GKLRQIIQRG GILITERKKA DFSTKDIYQD 250 260 270 280 290 300 LNRLLKGKKG EQMNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LTTFDFSQYM 310 320 330 340 350 360 KLDIAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTPQGQR LVNQWIKQPL MDKNRIEERL 370 380 390 400 410 420 NLVEAFVEDA ELRQTLQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG INQLPNVIQA 430 440 450 460 470 480 LEKHEGKHQK LLLAVFVTPL TDLRSDFSKF QEMIETTLDM DQVENHEFLV KPSFDPNLSE 490 500 510 520 530 540 LREIMNDLEK KMQSTLISAA RDLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS 550 560 570 580 590 600 TVDIQKNGVK FTNSKLTSLN EEYTKNKTEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA 610 620 630 640 650 660 QLDAVVSFAH VSNGAPVPYV RPAILEKGQG RIILKASRHA CVEVQDEIAF IPNDVYFEKD 670 680 690 700 710 720 KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK 730 740 750 760 770 780 GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISEYI ATKIGAFCMF 790 800 810 820 830 840 ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPKHV 850 860 870 880 890 900 IECAKQKALE LEEFQYIGES QGYDIMEPAA KKCYLEREQG EKIIQEFLSK VKQMPFTEMS 910 920 930 EENITIKLKQ LKAEVIAKNN SFVNEIISRI KVTT
	Isoform 2 [UniParc]. Checksum: 1BC5218379005E26	FASTA	868	97,323
	10 20 30 40 50 60 MGPAGAKNLQ SVVLSKMNFE SFVKDLLLVR QYRVEVYKNR AGNKASKEND WYLAYKASPG 70 80 90 100 110 120 NLSQFEDILF GNNDMSASIG VVGVKMSAVD GQRQVGVGYV DSIQRKLGLC EFPDNDQFSN 130 140 150 160 170 180 LEALLIQIGP KECVLPGGET AGDMGKLRQI IQRGGILITE RKKADFSTKD IYQDLNRLLK 190 200 210 220 230 240 GKKGEQMNSA VLPEMENQVA VSSLSAVIKF LELLSDDSNF GQFELTTFDF SQYMKLDIAA 250 260 270 280 290 300 VRALNLFQGS VEDTTGSQSL AALLNKCKTP QGQRLVNQWI KQPLMDKNRI EERLNLVEAF 310 320 330 340 350 360 VEDAELRQTL QEDLLRRFPD LNRLAKKFQR QAANLQDCYR LYQGINQLPN VIQALEKHEG 370 380 390 400 410 420 KHQKLLLAVF VTPLTDLRSD FSKFQEMIET TLDMDQVENH EFLVKPSFDP NLSELREIMN 430 440 450 460 470 480 DLEKKMQSTL ISAARDLGLD PGKQIKLDSS AQFGYYFRVT CKEEKVLRNN KNFSTVDIQK 490 500 510 520 530 540 NGVKFTNSKL TSLNEEYTKN KTEYEEAQDA IVKEIVNISS GYVEPMQTLN DVLAQLDAVV 550 560 570 580 590 600 SFAHVSNGAP VPYVRPAILE KGQGRIILKA SRHACVEVQD EIAFIPNDVY FEKDKQMFHI 610 620 630 640 650 660 ITGPNMGGKS TYIRQTGVIV LMAQIGCFVP CESAEVSIVD CILARVGAGD SQLKGVSTFM 670 680 690 700 710 720 AEMLETASIL RSATKDSLII IDELGRGTST YDGFGLAWAI SEYIATKIGA FCMFATHFHE 730 740 750 760 770 780 LTALANQIPT VNNLHVTALT TEETLTMLYQ VKKGVCDQSF GIHVAELANF PKHVIECAKQ 790 800 810 820 830 840 KALELEEFQY IGESQGYDIM EPAAKKCYLE REQGEKIIQE FLSKVKQMPF TEMSEENITI 850 860 KLKQLKAEVI AKNNSFVNEI ISRIKVTT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer." Fishel R., Lescoe M., Rao M., Copeland N.G., Jenkins N.A., Garber J., Kane M.F., Kolodner R.D. Cell 75:1027-1038(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	Erratum Fishel R., Lescoe M., Rao M., Copeland N.G., Jenkins N.A., Garber J., Kane M.F., Kolodner R.D. Cell 77:167-167(1994) [PubMed] [Europe PMC] [Abstract]
[3]	"Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer." Leach F.S., Nicolaides N.C., Papadopoulos N., Liu B., Jen J., Parsons R., Peltomaeki P., Sistonen P., Aaltonen L.A., Nystroem-Lahti M., Guan X.-Y., Zhang J., Meltzer P.S., Yu J.-W., Kao F.-T., Chen D.J., Cerosaletti K.M., Fournier R.E.K. , Todd S., Lewis T., Leach R.J., Naylor S.L., Weissenbach J., Mecklin J.-P., Jaervinen H., Petersen G.M., Hamilton S.R., Green J., Jass J., Watson P., Lynch H.T., Trent J.M., de la Chapelle A., Kinzler K.W., Vogelstein B. Cell 75:1215-1225(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS HNPCC1 LEU-622 AND TYR-639.
[4]	"Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations." Kolodner R.D., Hall N.R., Lipford J., Kane M.F., Rao M.R.S., Morrison P., Wirth L., Finan P.J., Burn J., Chapman P., Earabino C., Merchant E., Bishop D.T. Genomics 24:516-526(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INVOLVEMENT IN MRTES.
[5]	"Seven new mutations in hMSH2, an HNPCC gene, identified by denaturing gradient-gel electrophoresis." Wijnen J., Vasen H., Khan P.M., Menko F.H., van der Klift H., van Leeuwen C., van den Broek M., van Leeuwen-Cornelisse I., Nagengast F., Meijers-Heijboer A., Lindhout D., Griffioen G., Cats A., Kleibeuker J., Varesco L., Bertario L., Bisgaard M.-L., Mohr J., Fodde R. Am. J. Hum. Genet. 56:1060-1066(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT HIS-96.
[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: Uterus.
[7]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[8]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	NIEHS SNPs program Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-8; CYS-43; SER-127; ASP-322 AND PHE-390.
[10]	"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: Muscle.
[11]	"A novel germline mutation at exon 7 of the hMSH2 gene (417 del G) in a large HNPCC Brazilian kindred." Corvello C.M., Bevilacqua R.A.U., Rossi B.M., Simpson A.J.G. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 375-425. Tissue: Blood.
[12]	"Purified human MSH2 protein binds to DNA containing mismatched nucleotides." Fishel R., Ewel A., Lescoe M.K. Cancer Res. 54:5539-5542(1994) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING.
[13]	"A carboxy terminal domain of the hMSH-2 gene product is sufficient for binding specific mismatched oligonucleotides." Whitehouse A., Taylor G.R., Deeble J., Phillips S.E., Meredith D.M., Markham A.F. Biochem. Biophys. Res. Commun. 225:289-295(1996) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING.
[14]	"hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6." Acharya S., Wilson T., Gradia S., Kane M.F., Guerrette S., Marsischky G.T., Kolodner R.D., Fishel R. Proc. Natl. Acad. Sci. U.S.A. 93:13629-13634(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MSH3 AND MSH6.
[15]	"Human exonuclease I interacts with the mismatch repair protein hMSH2." Schmutte C., Marinescu R.C., Sadoff M.M., Guerrette S., Overhauser J., Fishel R. Cancer Res. 58:4537-4542(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EXO1.
[16]	"Nucleotide-promoted release of hMutSalpha from heteroduplex DNA is consistent with an ATP-dependent translocation mechanism." Blackwell L.J., Martik D., Bjornson K.P., Bjornson E.S., Modrich P. J. Biol. Chem. 273:32055-32062(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[17]	"DNA-dependent activation of the hMutSalpha ATPase." Blackwell L.J., Bjornson K.P., Modrich P. J. Biol. Chem. 273:32049-32054(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[18]	"hMSH2 and hMSH6 play distinct roles in mismatch binding and contribute differently to the ATPase activity of hMutSalpha." Iaccarino I., Marra G., Palombo F., Jiricny J. EMBO J. 17:2677-2686(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-675.
[19]	"Functional analysis of human MutSalpha and MutSbeta complexes in yeast." Clark A.B., Cook M.E., Tran H.T., Gordenin D.A., Resnick M.A., Kunkel T.A. Nucleic Acids Res. 27:736-742(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MISMATCH-BINDING, CHARACTERIZATION OF VARIANT HNPCC1 PRO-524.
[20]	"hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA." Gradia S., Subramanian D., Wilson T., Acharya S., Makhov A., Griffith J., Fishel R. Mol. Cell 3:255-261(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[21]	"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 MSH2 AS MEMBER OF BASC.
[22]	"Identification of factors interacting with hMSH2 in the fetal liver utilizing the yeast two-hybrid system. In vivo interaction through the C-terminal domains of hEXO1 and hMSH2 and comparative expression analysis." Rasmussen L.J., Rasmussen M., Lee B.-I., Rasmussen A.K., Wilson D.M. III, Nielsen F.C., Bisgaard H.C. Mutat. Res. 460:41-52(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EXO1, TISSUE SPECIFICITY.
[23]	"The role of mismatched nucleotides in activating the hMSH2-hMSH6 molecular switch." Gradia S., Acharya S., Fishel R. J. Biol. Chem. 275:3922-3930(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[24]	"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.
[25]	"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.
[26]	"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.
[27]	"MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation." Wang Y., Qin J. Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ATR, IDENTIFICATION BY MASS SPECTROMETRY.
[28]	"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.
[29]	"The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase." Yang Q., Zhang R., Wang X.W., Linke S.P., Sengupta S., Hickson I.D., Pedrazzi G., Perrera C., Stagljar I., Littman S.J., Modrich P., Harris C.C. Oncogene 23:3749-3756(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[30]	"hMutS alpha is protected from ubiquitin-proteasome-dependent degradation by atypical protein kinase C zeta phosphorylation." Hernandez-Pigeon H., Quillet-Mary A., Louat T., Schambourg A., Humbert O., Selves J., Salles B., Laurent G., Lautier D. J. Mol. Biol. 348:63-74(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY PRKCZ.
[31]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[32]	"The DNA-mismatch repair enzyme hMSH2 modulates UV-B-induced cell cycle arrest and apoptosis in melanoma cells." Seifert M., Scherer S.J., Edelmann W., Bohm M., Meineke V., Lobrich M., Tilgen W., Reichrath J. J. Invest. Dermatol. 128:203-213(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[33]	"Colon cancer and DNA repair: have mismatches met their match?" Jiricny J. Trends Genet. 10:164-168(1994) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[34]	"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.
[35]	"The role of the human DNA mismatch repair gene hMSH2 in DNA repair, cell cycle control and apoptosis: implications for pathogenesis, progression and therapy of cancer." Seifert M., Reichrath J. J. Mol. Histol. 37:301-307(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[36]	"The novel protein complex with SMARCAD1/KIAA1122 binds to the vicinity of TSS." Okazaki N., Ikeda S., Ohara R., Shimada K., Yanagawa T., Nagase T., Ohara O., Koga H. J. Mol. Biol. 382:257-265(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SMARCAD1.
[37]	"Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair." Svendsen J.M., Smogorzewska A., Sowa M.E., O'Connell B.C., Gygi S.P., Elledge S.J., Harper J.W. Cell 138:63-77(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SLX4.
[38]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-555, MASS SPECTROMETRY.
[39]	"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].
[40]	"Structure of the human MutSalpha DNA lesion recognition complex." Warren J.J., Pohlhaus T.J., Changela A., Iyer R.R., Modrich P.L., Beese L.S. Mol. Cell 26:579-592(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS).
[41]	"Mutational analysis of the hMSH2 gene reveals a three base pair deletion in a family predisposed to colorectal cancer development." Mary J.-L., Bishop T., Kolodner R.D., Lipford J.R., Kane M.F., Weber W., Torhorst J., Mueller H., Spycher M., Scott R.J. Hum. Mol. Genet. 3:2067-2069(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 ASN-596 DEL.
[42]	"Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer." Konishi M., Kikuchi-Yanoshita R., Tanaka K., Muraoka M., Onda A., Okumura Y., Kishi N., Iwama T., Mori T., Koike M., Ushio K., Chiba M., Nomizu S., Konishi F., Utsunomiya J., Miyaki M. Gastroenterology 111:307-317(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PHE-390 AND LYS-419.
[43]	"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: VARIANT ASP-322.
[44]	"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: VARIANT HNPCC1 ASN-596 DEL, VARIANT HIS-167.
[45]	"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: VARIANT CRC TYR-506.
[46]	"Microsatellite instability and the role of hMSH2 in sporadic colorectal cancer." Bubb V.J., Curtis L.J., Cunningham C., Dunlop M.G., Carothers A.D., Morris R.G., White S., Bird C.C., Wyllie A.H. Oncogene 12:2641-2649(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 GLN-46.
[47]	"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 HNPCC1 THR-305; ASN-596 DEL AND THR-834.
[48]	"Frequent somatic mutations of hMSH3 with reference to microsatellite instability in hereditary nonpolyposis colorectal cancers." Akiyama Y., Tsubouchi N., Yuasa Y. Biochem. Biophys. Res. Commun. 236:248-252(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 CYS-323.
[49]	"Identification of concurrent germ-line mutations in hMSH2 and/or hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds." Nakahara M., Yokozaki H., Yasui W., Dohi K., Tahara E. Cancer Epidemiol. Biomarkers Prev. 6:1057-1064(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HNPCC1 THR-110; ARG-639; LYS-647; HIS-656; THR-679; VAL-729 AND ILE-732.
[50]	"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 SER-596.
[51]	"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: VARIANT ASP-322.
[52]	"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 HNPCC1 VAL-562.
[53]	"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 HNPCC1 PHE-697, VARIANT ASP-322.
[54]	"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: VARIANT HNPCC1 265-VAL--GLN-314 DEL, VARIANTS GLY-641 AND VAL-770.
[55]	"Microsatellite instability and mutation of DNA mismatch repair genes in gliomas." Leung S.Y., Chan T.L., Chung L.P., Chan A.S.Y., Fan Y.W., Hung K.N., Kwong W.K., Ho J.W.C., Yuen S.T. Am. J. Pathol. 153:1181-1188(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLIOMA ARG-199.
[56]	"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 CRC TYR-506, VARIANT HNPCC1 ILE-688.
[57]	"MSH2 codon 322 Gly to Asp seems not to confer an increased risk for colorectal cancer susceptibility." Liu T., Stathopoulos P., Lindblom P., Rubio C., Wasteson Arver B., Iselius L., Holmberg E., Groenberg H., Lindblom A. Eur. J. Cancer 34:1981-1981(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ASP-322.
[58]	"Novel germline mutations of hMSH2 in a patient with hereditary nonpolyposis colorectal cancer 'HNPCC' and in a patient with six primary cancers." Okamura S., Koyama K., Miyoshi Y., Monden M., Takami M. J. Hum. Genet. 43:143-145(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PHE-390.
[59]	"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 HNPCC1 SER-336 AND ASN-596 DEL.
[60]	"Mutator phenotypes of common polymorphisms and missense mutations in MSH2." Drotschmann K., Clark A.B., Kunkel T.A. Curr. Biol. 9:907-910(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS ASP-322; PHE-390; LYS-419; TYR-506; PRO-524; LEU-622 AND PHE-697.
[61]	"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 HNPCC1 GLN-246; ASP-322; SER-596 AND THR-834.
[62]	"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 HNPCC1 PHE-390.
[63]	"A missense mutation in both hMSH2 and APC in an Ashkenazi Jewish HNPCC kindred: implications for clinical screening." Yuan Z.Q., Wong N., Foulkes W.D., Alpert L., Manganaro F., Andreutti-Zaugg C., Iggo R., Anthony K., Hsieh E., Redston M., Pinsky L., Trifiro M., Gordon P.H., Lasko D. J. Med. Genet. 36:790-793(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 PRO-636.
[64]	"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 HNPCC1 ILE-688 AND GLU-845, VARIANT MET-8.
[65]	"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: VARIANT ASP-322.
[66]	"Four novel MSH2 / MLH1 gene mutations in Portuguese HNPCC families." Isidro G., Veiga I., Matos P., Almeida S., Bizarro S., Marshall B., Baptista M., Leite J., Regateiro F., Soares J., Castedo S., Boavida M.G. Hum. Mutat. 15:116-116(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HNPCC1 ARG-692 AND ARG-697.
[67]	"Population-based molecular detection of hereditary nonpolyposis colorectal cancer." Salovaara R., Loukola A., Kristo P., Kaeaeriaeinen H., Ahtola H., Eskelinen M., Haerkoenen N., Julkunen R., Kangas E., Ojala S., Tulikoura J., Valkamo E., Jaervinen H., Mecklin J.-P., Aaltonen L.A., de la Chapelle A. J. Clin. Oncol. 18:2193-2200(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 ASN-603, VARIANT ASP-322.
[68]	Erratum Salovaara R., Loukola A., Kristo P., Kaeaeriaeinen H., Ahtola H., Eskelinen M., Haerkoenen N., Julkunen R., Kangas E., Ojala S., Tulikoura J., Valkamo E., Jaervinen H., Mecklin J.-P., Aaltonen L.A., de la Chapelle A. J. Clin. Oncol. 18:3456-3456(2000)
[69]	"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 PHE-17; GLU-824; ALA-868; GLY-870 AND GLY-873, VARIANTS HNPCC1 CYS-98; TYR-323; ILE-335; ARG-629 AND VAL-714.
[70]	"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 HNPCC1 ASP-161; VAL-216 AND ARG-554.
[71]	"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 ASP-322; LEU-622 AND TYR-639.
[72]	"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: VARIANT HNPCC1 VAL-813.
[73]	"Evaluation of screening strategy for detecting hereditary nonpolyposis colorectal carcinoma." Furukawa T., Konishi F., Shitoh K., Kojima M., Nagai H., Tsukamoto T. Cancer 94:911-920(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HNPCC1 VAL-600 AND PHE-723.
[74]	"HNPCC mutations in hMSH2 result in reduced hMSH2-hMSH6 molecular switch functions." Heinen C.D., Wilson T., Mazurek A., Berardini M., Butz C., Fishel R. Cancer Cell 1:469-478(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HNPCC1 HIS-167; MET-393; PRO-524; ASN-596 DEL; LEU-622; SER-674 AND ARG-905, CHARACTERIZATION OF VARIANTS HNPCC1 HIS-167; MET-393; PRO-524; ASN-596 DEL; LEU-622; SER-674 AND ARG-905.
[75]	"A homozygous germ-line mutation in the human MSH2 gene predisposes to hematological malignancy and multiple cafe-au-lait spots." Whiteside D., McLeod R., Graham G., Steckley J.L., Booth K., Somerville M.J., Andrew S.E. Cancer Res. 62:359-362(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MULTIPLE CAFE-AU-LAIT SPOTS WITH LEUKEMIA.
[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: VARIANT ASP-322.
[77]	"Hereditary non-polyposis colorectal cancer (HNPCC): phenotype-genotype correlation between patients with and without identified mutation." Bisgaard M.L., Jaeger A.C., Myrhoej T., Bernstein I., Nielsen F.C. Hum. Mutat. 20:20-27(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HNPCC1 MET-44; VAL-45; ASN-596 DEL; GLY-886 AND GLU-923.
[78]	"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 HNPCC1 ILE-102; ASP-163 AND ALA-564, VARIANT ASP-322.
[79]	"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: VARIANTS HNPCC1 HIS-167 AND SER-359.
[80]	"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 HNPCC1 LEU-92 DEL AND ALA-853, VARIANT ASP-322.
[81]	"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 HNPCC1 PRO-552; SER-583 AND PRO-636.
[82]	"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 ILE-13 AND ILE-342, VARIANT ASP-322.
[83]	"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 HNPCC1 SER-127.
[84]	"Novel MLH1 and MSH2 germline mutations in the first HNPCC families identified in Slovakia." Bartosova Z., Fridrichova I., Bujalkova M., Wolf B., Ilencikova D., Krizan P., Hlavcak P., Palaj J., Lukac L., Lukacova M., Boeoer A., Haider R., Jiricny J., Nystroem-Lahti M., Marra G. Hum. Mutat. 21:449-449(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 PRO-175.
[85]	"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 HNPCC1 GLY-163 AND GLY-660.
[86]	"Oncogenic pathway of sporadic colorectal cancer with novel germline missense mutations in the hMSH2 gene." Yamada K., Zhong X., Kanazawa S., Koike J., Tsujita K., Hemmi H. Oncol. Rep. 10:859-866(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CRC MET-8; SER-40; VAL-169; ARG-203; PHE-390; LYS-419; CYS-619 AND ARG-629.
[87]	"Gene symbol: hMSH2. Disease: hereditary nonpolyposis colorectal cancer." Sun M.H., Cai Q., Fu G., Ren S., Mo S., Xu Y., Ding C., Zhang T., Zhu X., Xu X., Min D., Cai S., Luo D., Shi Y., Shi D. Hum. Genet. 114:409-409(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 THR-931.
[88]	"RNA analysis reveals splicing mutations and loss of expression defects in MLH1 and BRCA1." Sharp A., Pichert G., Lucassen A., Eccles D. Hum. Mutat. 24:272-272(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 TYR-671.
[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 HNPCC1 LEU-440 DEL; TYR-506; ARG-629 AND ILE-688.
[90]	"Genetic characterization of Chinese hereditary non-polyposis colorectal cancer by DHPLC and multiplex PCR." Yuan Y., Huang Y.-Q., Cai S.-R., Song Y.-M., Zheng S., Zhang S.-Z. Jpn. J. Clin. Oncol. 34:660-666(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 ARG-839, VARIANT ARG-629.
[91]	"BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing." Domingo E., Laiho P., Ollikainen M., Pinto M., Wang L., French A.J., Westra J., Frebourg T., Espin E., Armengol M., Hamelin R., Yamamoto H., Hofstra R.M.W., Seruca R., Lindblom A., Peltomaeki P., Thibodeau S.N., Aaltonen L.A., Schwartz S. Jr. J. Med. Genet. 41:664-668(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HNPCC1 LEU-349 AND ASN-596 DEL.
[92]	"A novel missense germline mutation in exon 2 of the hMSH2 gene in a HNPCC family from Southern Italy." Baudi F., Fersini G., Lavecchia A., Terracciano R., Leone F., Quaresima B., Faniello M.C., De Paola L., Doldo P., Cuda G., Costanzo F., Venuta S. Cancer Lett. 223:285-291(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 PHE-93.
[93]	"Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia." Lee S.-C., Guo J.-Y., Lim R., Soo R., Koay E., Salto-Tellez M., Leong A., Goh B.-C. Clin. Genet. 68:137-145(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HNPCC1 VAL-169; PHE-390; ALA-564 AND ARG-629, VARIANT CRC LYS-419.
[94]	"Hereditary nonpolyposis colorectal cancer: pitfalls in deletion screening in MSH2 and MLH1 genes." Wehner M., Mangold E., Sengteller M., Friedrichs N., Aretz S., Friedl W., Propping P., Pagenstecher C. Eur. J. Hum. Genet. 13:983-986(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 TYR-283.
[95]	"Gene symbol: MSH2. Disease: hereditary nonpolyposis colorectal cancer." Kohonen-Corish M.R.J., Otway R., Tetlow N., Hornby J., Doe W.F. Hum. Genet. 116:539-539(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 ARG-162.
[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 HNPCC1 THR-2; LEU-92 DEL; MET-145; PHE-390 AND ALA-853, VARIANT ASP-322.
[97]	"Pathogenicity of MSH2 missense mutations is typically associated with impaired repair capability of the mutated protein." Ollila S., Sarantaus L., Kariola R., Chan P., Hampel H., Holinski-Feder E., Macrae F., Kohonen-Corish M., Gerdes A.-M., Peltomaeki P., Mangold E., de la Chapelle A., Greenblatt M., Nystroem M. Gastroenterology 131:1408-1417(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HNPCC1 PRO-33; ASP-161; ARG-162; ARG-164; PRO-173; PRO-187; TYR-333; ASN-603; PRO-636; PHE-697; 745-ILE-ILE-746 DEL AND LYS-749, VARIANTS VAL-272; THR-834 AND GLU-923, CHARACTERIZATION OF VARIANTS HNPCC1 PRO-33; ASP-161; ARG-162; ARG-164; PRO-173; PRO-187; TYR-333; ASN-603; PRO-636; PHE-697; 745-ILE-ILE-746 DEL AND LYS-749, CHARACTERIZATION OF VARIANTS VAL-272; THR-834 AND GLU-923.
[98]	"Gene symbol: msh2. Disease: hereditary nonpolyposis colorectal cancer." Leonardis D. Hum. Genet. 119:675-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 ALA-162.
[99]	"A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting." Ramsoekh D., Wagner A., van Leerdam M.E., Dinjens W.N., Steyerberg E.W., Halley D.J., Kuipers E.J., Dooijes D. Gut 57:1539-1544(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 ARG-674.
[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 GLN-46; LYS-106; ASP-322; SER-596; LEU-670; ILE-779; SER-807; HIS-835 AND ARG-911.
[101]	"Mechanisms of pathogenicity in human MSH2 missense mutants." Ollila S., Dermadi Bebek D., Jiricny J., Nystroem M. Hum. Mutat. 29:1355-1363(2008) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF GLY-674, CHARACTERIZATION OF VARIANTS HNPCC1 PRO-33; SER-127; ASP-161; ARG-162; ARG-164; PRO-173; PRO-187; TYR-333; ASN-603; PRO-636; PHE-697; 745-ILE-ILE-746 DEL; LYS-749; THR-834 AND GLU-923, CHARACTERIZATION OF VARIANTS VAL-272 AND ASP-322.
[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: VARIANTS HNPCC1 LEU-92 DEL AND ARG-199, VARIANTS VAL-272; ASP-331; GLU-470; ASN-596 DEL; ASN-610; GLY-638; GLU-645; TYR-671; LEU-696; ARG-697; PHE-723; TYR-748 AND GLN-839, CHARACTERIZATION OF VARIANTS HNPCC1 LEU-92 DEL AND ARG-199, CHARACTERIZATION OF VARIANTS VAL-272; ASP-331; GLU-470; ASN-596 DEL; ASN-610; GLY-638; GLU-645; TYR-671; LEU-696; ARG-697; PHE-723; TYR-748 AND GLN-839.
[103]	"MSH2 missense mutations and HNPCC syndrome: pathogenicity assessment in a human expression system." Belvederesi L., Bianchi F., Galizia E., Loretelli C., Bracci R., Catalani R., Amati M., Cellerino R. Hum. Mutat. 29:E296-E309(2008) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS HNPCC1 ARG-162; HIS-167 AND SER-359.
[104]	"Functional analysis of HNPCC-related missense mutations in MSH2." Lutzen A., de Wind N., Georgijevic D., Nielsen F.C., Rasmussen L.J. Mutat. Res. 645:44-55(2008) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS HNPCC1 HIS-167; THR-305: LEU-622; ARG-639; ARG-674; PHE-697 AND THR-834.
[105]	"A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants." Drost M., Zonneveld J.B., van Hees S., Rasmussen L.J., Hofstra R.M., de Wind N. Hum. Mutat. 33:488-494(2012) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS HNPCC1 MET-44; VAL-45; HIS-167; THR-305; PHE-390; ASN-596 DEL; ARG-639; ARG-674; PHE-697; PHE-723 AND GLY-886, CHARACTERIZATION OF VARIANTS ASP-165; HIS-177; VAL-272; LEU-385; LEU-519; ALA-675; GLU-759; VAL-805; GLY-843 AND LEU-860.
[106]	"Mismatch repair analysis of inherited MSH2 and/or MSH6 variation pairs found in cancer patients." Kantelinen J., Kansikas M., Candelin S., Hampel H., Smith B., Holm L., Kariola R., Nystrom M. Hum. Mutat. 33:1294-1301(2012) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS SER-127; MET-145; GLN-205; ASP-322; PRO-328; ILE-367; GLU-487 AND ILE-909.
[107]	"Germline mutation analysis of MLH1 and MSH2 in Malaysian Lynch syndrome patients." Zahary M.N., Kaur G., Abu Hassan M.R., Singh H., Naik V.R., Ankathil R. World J. Gastroenterol. 18:814-820(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HNPCC1 ARG-669.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Hereditary non-polyposis colorectal cancer db

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U03911 mRNA. Translation: AAA18643.1.
U04045 mRNA. Translation: AAA61870.1.
U41221 , U41206, U41207, U41208, U41210, U41211, U41212, U41213, U41214, U41215, U41216, U41217, U41218, U41219, U41220 Genomic DNA. Translation: AAA82080.1. Sequence problems.
L47583 mRNA. Translation: AAB59564.1.
L47582 mRNA. Translation: AAB59565.1.
L47581 mRNA. Translation: AAA76858.1.
AY601851 Genomic DNA. Translation: AAS99351.1.
AK304496 mRNA. Translation: BAG65304.1.
BX649122 mRNA. No translation available.
AC079775 Genomic DNA. No translation available.
AC138655 Genomic DNA. No translation available.
BC021566 mRNA. Translation: AAH21566.1.
AF066081 Genomic DNA. Translation: AAC27930.1. Frameshift.

IPI

IPI00017303.
IPI01014700.

PIR

I64819.

RefSeq

NP_000242.1. NM_000251.2.
NP_001245210.1. NM_001258281.1.

UniGene

Hs.597656.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2O8B	X-ray	2.75	A	1-934	[»]
2O8C	X-ray	3.37	A	1-934	[»]
2O8D	X-ray	3.00	A	1-934	[»]
2O8E	X-ray	3.30	A	1-934	[»]
2O8F	X-ray	3.25	A	1-934	[»]
3THW	X-ray	3.09	A	1-934	[»]
3THX	X-ray	2.70	A	1-934	[»]
3THY	X-ray	2.89	A	1-934	[»]
3THZ	X-ray	4.30	A	1-934	[»]

ProteinModelPortal

P43246.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35054N.

IntAct

P43246. 12 interactions.

MINT

MINT-84789.

STRING

9606.ENSP00000233146.

PTM databases

PhosphoSite

P43246.

Polymorphism databases

DMDM

1171032.

Proteomic databases

PaxDb

P43246.

PeptideAtlas

P43246.

PRIDE

P43246.

Protocols and materials databases

DNASU

4436.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000233146; ENSP00000233146; ENSG00000095002.
ENST00000543555; ENSP00000442697; ENSG00000095002.

GeneID

4436.

KEGG

hsa:4436.

UCSC

uc002rvy.1. human.

Organism-specific databases

CTD

4436.

GeneCards

GC02P047630.

HGNC

HGNC:7325. MSH2.

HPA

CAB009572.

MIM

120435. phenotype.
158320. phenotype.
608089. phenotype.
609309. gene.

neXtProt

NX_P43246.

Orphanet

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

PharmGKB

PA31133.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0249.

HOGENOM

HOG000196498.

HOVERGEN

HBG006399.

InParanoid

P43246.

KO

K08735.

OMA

WAISEHI.

OrthoDB

EOG4D26P5.

PhylomeDB

P43246.

Gene expression databases

ArrayExpress

P43246.

Bgee

P43246.

CleanEx

HS_MSH2.

Genevestigator

P43246.

GermOnline

ENSG00000095002. Homo sapiens.

Family and domain databases

InterPro

IPR011184. DNA_mismatch_repair_MSH2.
IPR007695. DNA_mismatch_repair_MutS-lik_N.
IPR000432. DNA_mismatch_repair_MutS_C.
IPR007861. DNA_mismatch_repair_MutS_clamp.
IPR007696. DNA_mismatch_repair_MutS_core.
IPR007860. DNA_mmatch_repair_MutS_con_dom.
[Graphical view]

Pfam

PF01624. MutS_I. 1 hit.
PF05188. MutS_II. 1 hit.
PF05192. MutS_III. 1 hit.
PF05190. MutS_IV. 1 hit.
PF00488. MutS_V. 1 hit.
[Graphical view]

PIRSF

PIRSF005813. MSH2. 1 hit.

SMART

SM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]

SUPFAM

SSF48334. DNA_repair_MutS_domIII. 1 hit.

PROSITE

PS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

MSH2. human.

EvolutionaryTrace

P43246.

GenomeRNAi

4436.

NextBio

17289.

SOURCE

Search...

Entry information

Entry name

MSH2_HUMAN

Accession

Primary (citable) accession number: P43246
Secondary accession number(s): B4E2Z2, O75488

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 153 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.