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P43246

- MSH2_HUMAN

UniProt

P43246 - MSH2_HUMAN

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Protein

DNA mismatch repair protein Msh2

Gene

MSH2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.7 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi669 – 6768ATPSequence Analysis

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. centromeric DNA binding Source: Ensembl
  3. damaged DNA binding Source: Ensembl
  4. DNA binding Source: UniProtKB
  5. DNA-dependent ATPase activity Source: RefGenome
  6. double-strand/single-strand DNA junction binding Source: RefGenome
  7. enzyme binding Source: UniProtKB
  8. guanine/thymine mispair binding Source: MGI
  9. heteroduplex DNA loop binding Source: RefGenome
  10. protein C-terminus binding Source: UniProtKB
  11. protein homodimerization activity Source: HGNC
  12. protein kinase binding Source: UniProtKB
  13. Y-form DNA binding Source: RefGenome

GO - Biological processi

  1. ATP catabolic process Source: GOC
  2. B cell differentiation Source: BHF-UCL
  3. B cell mediated immunity Source: BHF-UCL
  4. cell cycle arrest Source: Ensembl
  5. determination of adult lifespan Source: Ensembl
  6. DNA repair Source: BHF-UCL
  7. double-strand break repair Source: RefGenome
  8. germ cell development Source: Ensembl
  9. intra-S DNA damage checkpoint Source: RefGenome
  10. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: RefGenome
  11. in utero embryonic development Source: Ensembl
  12. isotype switching Source: BHF-UCL
  13. maintenance of DNA repeat elements Source: HGNC
  14. male gonad development Source: BHF-UCL
  15. meiotic gene conversion Source: RefGenome
  16. meiotic mismatch repair Source: RefGenome
  17. mismatch repair Source: UniProtKB
  18. negative regulation of DNA recombination Source: BHF-UCL
  19. negative regulation of neuron apoptotic process Source: BHF-UCL
  20. negative regulation of reciprocal meiotic recombination Source: RefGenome
  21. oxidative phosphorylation Source: Ensembl
  22. positive regulation of helicase activity Source: BHF-UCL
  23. postreplication repair Source: UniProtKB
  24. response to UV-B Source: BHF-UCL
  25. response to X-ray Source: BHF-UCL
  26. somatic hypermutation of immunoglobulin genes Source: RefGenome
  27. somatic recombination of immunoglobulin gene segments Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_228019. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
REACT_228145. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein Msh2
Short name:
hMSH2
Alternative name(s):
MutS protein homolog 2
Gene namesi
Name:MSH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:7325. MSH2.

Subcellular locationi

Nucleus Curated

GO - Cellular componenti

  1. membrane Source: UniProtKB
  2. MutSalpha complex Source: UniProtKB
  3. MutSbeta complex Source: HGNC
  4. nuclear chromosome Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

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.46 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti2 – 21A → T in HNPCC1. 1 Publication
VAR_054511
Natural varianti33 – 331T → P in HNPCC1; shows slightly reduced mismatch binding or release efficiency. 1 Publication
VAR_043738
Natural varianti44 – 441T → M in HNPCC1; repair proficient. 1 Publication
VAR_043740
Natural varianti45 – 451A → V in HNPCC1; repair proficient. 1 Publication
VAR_043741
Natural varianti46 – 461H → Q in HNPCC1. 2 Publications
Corresponds to variant rs33946261 [ dbSNP | Ensembl ].
VAR_004470
Natural varianti92 – 921Missing in HNPCC1; unknown pathological significance. 3 Publications
VAR_043742
Natural varianti93 – 931L → F in HNPCC1. 1 Publication
VAR_043743
Natural varianti98 – 981Y → C in HNPCC1; unknown pathological significance. 1 Publication
VAR_043744
Natural varianti102 – 1021V → I in HNPCC1. 1 Publication
VAR_043745
Natural varianti110 – 1101K → T in HNPCC1; somatic mutation. 1 Publication
VAR_043746
Natural varianti127 – 1271N → 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. 2 Publications
Corresponds to variant rs17217772 [ dbSNP | Ensembl ].
VAR_019234
Natural varianti139 – 1391N → S in HNPCC1.
VAR_004472
Natural varianti145 – 1451I → M in HNPCC1; mismatch repair proficient. 1 Publication
Corresponds to variant rs63750124 [ dbSNP | Ensembl ].
VAR_004473
Natural varianti161 – 1611V → D in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. 2 Publications
VAR_012936
Natural varianti162 – 1621G → A in HNPCC1. 1 Publication
VAR_054512
Natural varianti162 – 1621G → 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. 2 Publications
VAR_043747
Natural varianti163 – 1631V → D in HNPCC1. 1 Publication
VAR_043748
Natural varianti163 – 1631V → G in HNPCC1. 1 Publication
VAR_022670
Natural varianti164 – 1641G → R in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. 1 Publication
VAR_043749
Natural varianti165 – 1651Y → D Associated with HNPCC1; unknown pathological significance; repair deficient.
VAR_067284
Natural varianti167 – 1671D → 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. 3 Publications
VAR_004474
Natural varianti169 – 1691I → V in HNPCC1; unknown pathological significance. 2 Publications
Corresponds to variant rs63750716 [ dbSNP | Ensembl ].
VAR_043750
Natural varianti173 – 1731L → P in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. 1 Publication
VAR_043751
Natural varianti175 – 1751L → P in HNPCC1. 1 Publication
VAR_043752
Natural varianti177 – 1771E → H Associated with HNPCC1; requires 2 nucleotide substitutions; unknown pathological significance; repair proficient.
VAR_067285
Natural varianti187 – 1871L → P in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. 1 Publication
VAR_043753
Natural varianti198 – 1981E → G in HNPCC1.
VAR_054513
Natural varianti199 – 1991C → R in glioma; also associated with HNPCC1; has no effect on ex vivo splicing assay. 2 Publications
VAR_012937
Natural varianti216 – 2161I → V in HNPCC1; unknown pathological significance; shows slightly reduced mismatch binding or release efficiency. 1 Publication
VAR_012938
Natural varianti246 – 2461K → Q in HNPCC1; unknown pathological significance. 1 Publication
VAR_043755
Natural varianti265 – 31450Missing in HNPCC1. 1 Publication
VAR_004475Add
BLAST
Natural varianti272 – 2721A → 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. 2 Publications
Corresponds to variant rs34136999 [ dbSNP | Ensembl ].
VAR_043756
Natural varianti283 – 2831D → Y in HNPCC1. 1 Publication
VAR_043757
Natural varianti305 – 3051A → T in HNPCC1; repair proficient. 1 Publication
VAR_004476
Natural varianti323 – 3231S → C in HNPCC1; unknown pathological significance. 1 Publication
VAR_012939
Natural varianti323 – 3231S → Y in HNPCC1; unknown pathological significance. 1 Publication
VAR_043758
Natural varianti331 – 3311N → D Associated with HNPCC1; has no effect on ex vivo splicing assay. 1 Publication
VAR_054514
Natural varianti333 – 3331C → Y in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. 1 Publication
VAR_043759
Natural varianti335 – 3351T → I in HNPCC1; unknown pathological significance. 1 Publication
VAR_043760
Natural varianti336 – 3361P → S in HNPCC1. 1 Publication
VAR_043761
Natural varianti349 – 3491P → L in HNPCC1. 1 Publication
VAR_043763
Natural varianti359 – 3591R → S in HNPCC1; shows a decreased expression level of the MutS alpha comp lex and is associated with an abnormal subcellular localization pattern. 1 Publication
VAR_043764
Natural varianti385 – 3851P → L Associated with HNPCC1; unknown pathological significance; repair proficient.
VAR_067286
Natural varianti390 – 3901L → F in HNPCC1; unknown pathological significance; the equivalent substitution in yeast partially affects mismatch repair in vitro; repair proficient. 7 Publications
Corresponds to variant rs17224367 [ dbSNP | Ensembl ].
VAR_004478
Natural varianti393 – 3931K → M in HNPCC1. 1 Publication
VAR_043765
Natural varianti440 – 4401Missing in HNPCC1. 1 Publication
VAR_043766
Natural varianti470 – 4701V → E Associated with HNPCC1; has no effect on ex vivo splicing assay. 1 Publication
VAR_054515
Natural varianti492 – 4921M → V in HNPCC1.
VAR_043767
Natural varianti519 – 5191F → L Associated with HNPCC1; unknown pathological significance; repair proficient.
VAR_067287
Natural varianti524 – 5241R → P in HNPCC1; defective in mismatch repair activity. 1 Publication
VAR_004479
Natural varianti552 – 5521T → P in HNPCC1. 1 Publication
VAR_043768
Natural varianti554 – 5541S → R in HNPCC1; unknown pathological significance. 1 Publication
VAR_012942
Natural varianti562 – 5621E → V in HNPCC1. 1 Publication
VAR_004480
Natural varianti564 – 5641T → A in HNPCC1; unknown pathological significance. 2 Publications
Corresponds to variant rs55778204 [ dbSNP | Ensembl ].
VAR_043769
Natural varianti583 – 5831N → S in HNPCC1. 1 Publication
VAR_043770
Natural varianti596 – 5961N → S in HNPCC1; unknown pathological significance. 3 Publications
Corresponds to variant rs41295288 [ dbSNP | Ensembl ].
VAR_012943
Natural varianti596 – 5961Missing in HNPCC1; has no effect on ex vivo splicing assay; repair deficient. 8 Publications
VAR_004481
Natural varianti600 – 6001A → V in HNPCC1. 1 Publication
VAR_043771
Natural varianti603 – 6031D → N in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. 2 Publications
VAR_043772
Natural varianti610 – 6101H → N Associated with HNPCC1; has no effect on ex vivo splicing assay. 1 Publication
VAR_054516
Natural varianti622 – 6221P → L in HNPCC1; the equivalent substitution in yeast causes loss of function in a mismatch repair assay; confers multiple biochemical defects. 2 Publications
Corresponds to variant rs28929483 [ dbSNP | Ensembl ].
VAR_004482
Natural varianti629 – 6291Q → R in HNPCC1; unknown pathological significance. 5 Publications
Corresponds to variant rs61756468 [ dbSNP | Ensembl ].
VAR_043774
Natural varianti636 – 6361A → P in HNPCC1; partial functional loss; mainly causes defects in mismatch binding or release efficiency. 3 Publications
VAR_012944
Natural varianti638 – 6381R → G Associated with HNPCC1; has no effect on ex vivo splicing assay. 1 Publication
VAR_054517
Natural varianti639 – 6391H → R in HNPCC1; shows reduced mismatch binding; repair proficient. 1 Publication
VAR_043775
Natural varianti639 – 6391H → Y in HNPCC1; the equivalent substitution in yeast does not affect mismatch repair efficiency in vitro. 1 Publication
Corresponds to variant rs28929484 [ dbSNP | Ensembl ].
VAR_004483
Natural varianti645 – 6451Q → E Associated with HNPCC1; has no effect on ex vivo splicing assay. 1 Publication
VAR_054518
Natural varianti647 – 6471E → K in HNPCC1. 1 Publication
VAR_043776
Natural varianti656 – 6561Y → H in HNPCC1; somatic mutation. 1 Publication
VAR_043777
Natural varianti660 – 6601D → G in HNPCC1. 1 Publication
VAR_022671
Natural varianti669 – 6691G → R in HNPCC1. 1 Publication
VAR_067761
Natural varianti671 – 6711N → Y in HNPCC1; unknown pathological significance. 2 Publications
VAR_043778
Natural varianti674 – 6741G → R in HNPCC1; confers resistance to ATP-dependent mismatch release; repair deficient. 1 Publication
VAR_067288
Natural varianti674 – 6741G → S in HNPCC1; somatic mutation. 1 Publication
VAR_004485
Natural varianti675 – 6751K → A Associated with HNPCC1; requires 2 nucleotide substitutions; unknown pathological significance; repair deficient.
VAR_067289
Natural varianti679 – 6791I → T in HNPCC1; somatic mutation. 1 Publication
VAR_043779
Natural varianti688 – 6881M → I in HNPCC1. 3 Publications
Corresponds to variant rs63750790 [ dbSNP | Ensembl ].
VAR_012945
Natural varianti692 – 6921G → R in HNPCC1. 1 Publication
VAR_009250
Natural varianti696 – 6961P → L Associated with HNPCC1; has no effect on ex vivo splicing assay. 1 Publication
VAR_054519
Natural varianti697 – 6971C → 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. 2 Publications
VAR_004486
Natural varianti697 – 6971C → R in HNPCC1; has no effect on ex vivo splicing assay. 2 Publications
VAR_009251
Natural varianti714 – 7141A → V in HNPCC1; unknown pathological significance. 1 Publication
VAR_043780
Natural varianti723 – 7231S → F in HNPCC1; has no effect on ex vivo splicing assay; repair deficient. 2 Publications
VAR_043781
Natural varianti729 – 7291M → V in HNPCC1; somatic mutation. 1 Publication
VAR_043782
Natural varianti732 – 7321T → I in HNPCC1; somatic mutation. 1 Publication
VAR_043783
Natural varianti745 – 7462Missing in HNPCC1; mainly causes defects in mismatch binding or release efficiency. 1 Publication
VAR_043784
Natural varianti748 – 7481D → Y Associated with HNPCC1; has no effect on ex vivo splicing assay. 1 Publication
VAR_054520
Natural varianti749 – 7491E → K in HNPCC1; mainly causes defects in mismatch binding or release efficiency; the mutant protein is well expressed in tumors. 1 Publication
VAR_043785
Natural varianti759 – 7591G → E Associated with HNPCC1; unknown pathological significance; repair deficient.
VAR_067290
Natural varianti805 – 8051L → V Associated with HNPCC1; unknown pathological significance; repair proficient.
VAR_067291
Natural varianti813 – 8131M → V in HNPCC1. 1 Publication
VAR_043786
Natural varianti834 – 8341A → T in HNPCC1; shows no functional defects in gel shift assay; is nevertheless repair deficient. 3 Publications
VAR_004488
Natural varianti839 – 8391H → Q Associated with HNPCC1; has no effect on ex vivo splicing assay. 1 Publication
VAR_054521
Natural varianti839 – 8391H → R in HNPCC1. 1 Publication
VAR_043788
Natural varianti843 – 8431C → G Associated with HNPCC1; unknown pathological significance; repair proficient.
VAR_067292
Natural varianti845 – 8451K → E in HNPCC1. 1 Publication
Corresponds to variant rs63750571 [ dbSNP | Ensembl ].
VAR_013172
Natural varianti853 – 8531E → A in HNPCC1; unknown pathological significance. 2 Publications
VAR_043789
Natural varianti860 – 8601S → L Associated with HNPCC1; unknown pathological significance; repair proficient.
VAR_067293
Natural varianti886 – 8861E → G in HNPCC1; repair proficient. 1 Publication
VAR_043793
Natural varianti905 – 9051T → R in HNPCC1; unknown pathological significance. 1 Publication
VAR_004489
Natural varianti923 – 9231V → E in HNPCC1; unknown pathological significance. 2 Publications
VAR_043794
Natural varianti931 – 9311K → T in HNPCC1. 1 Publication
VAR_043795
Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
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.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi674 – 6741G → A: Mainly causes defects in mismatch binding or release efficiency. 1 Publication
Mutagenesisi675 – 6751K → R: No effect on mismatch binding, complete loss of DNA repair function when associated with MSH6 mutant R-1140. 1 Publication

Keywords - Diseasei

Disease mutation, Hereditary nonpolyposis colorectal cancer, Tumor suppressor

Organism-specific databases

MIMi120435. phenotype.
158320. phenotype.
608089. phenotype.
Orphaneti252202. Constitutional mismatch repair deficiency syndrome.
144. Hereditary nonpolyposis colon cancer.
587. Muir-Torre syndrome.
99817. Non-polyposis Turcot syndrome.
PharmGKBiPA31133.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 934933DNA mismatch repair protein Msh2PRO_0000115183Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei555 – 5551N6-acetyllysine1 Publication
Modified residuei567 – 5671N6-acetyllysineBy similarity

Post-translational modificationi

Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP43246.
PaxDbiP43246.
PeptideAtlasiP43246.
PRIDEiP43246.

PTM databases

PhosphoSiteiP43246.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiP43246.
CleanExiHS_MSH2.
ExpressionAtlasiP43246. baseline and differential.
GenevestigatoriP43246.

Organism-specific databases

HPAiCAB009572.

Interactioni

Subunit structurei

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 SMARCAD1.10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
E2F3O007162EBI-355888,EBI-765551
EXO1P398752EBI-355888,EBI-6738From a different organism.
EXO1Q9UQ84-13EBI-355888,EBI-944694
MSH3P205854EBI-355888,EBI-1164205
MSH6P527015EBI-355888,EBI-395529
SLX4Q8IY925EBI-355888,EBI-2370740

Protein-protein interaction databases

BioGridi110573. 95 interactions.
DIPiDIP-35054N.
IntActiP43246. 24 interactions.
MINTiMINT-84789.
STRINGi9606.ENSP00000233146.

Structurei

Secondary structure

1
934
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi14 – 2411Combined sources
Beta strandi33 – 386Combined sources
Beta strandi40 – 467Combined sources
Helixi48 – 569Combined sources
Beta strandi59 – 613Combined sources
Beta strandi65 – 717Combined sources
Beta strandi75 – 817Combined sources
Helixi82 – 9413Combined sources
Beta strandi99 – 1057Combined sources
Beta strandi117 – 1248Combined sources
Helixi129 – 1313Combined sources
Helixi132 – 1354Combined sources
Beta strandi147 – 1526Combined sources
Beta strandi155 – 1584Combined sources
Beta strandi160 – 1678Combined sources
Turni168 – 1714Combined sources
Beta strandi172 – 1798Combined sources
Helixi185 – 19410Combined sources
Beta strandi197 – 2048Combined sources
Helixi208 – 22013Combined sources
Beta strandi223 – 2275Combined sources
Helixi229 – 2324Combined sources
Helixi237 – 2448Combined sources
Turni252 – 2543Combined sources
Helixi255 – 2573Combined sources
Helixi259 – 2624Combined sources
Helixi264 – 27714Combined sources
Helixi279 – 2813Combined sources
Helixi283 – 2853Combined sources
Beta strandi289 – 2935Combined sources
Helixi296 – 2983Combined sources
Helixi304 – 3096Combined sources
Helixi326 – 3305Combined sources
Helixi336 – 34712Combined sources
Helixi353 – 36715Combined sources
Helixi370 – 3778Combined sources
Turni378 – 3803Combined sources
Helixi381 – 3833Combined sources
Helixi387 – 3959Combined sources
Helixi401 – 41111Combined sources
Helixi414 – 42310Combined sources
Beta strandi424 – 4263Combined sources
Beta strandi427 – 4293Combined sources
Helixi432 – 4354Combined sources
Helixi437 – 45519Combined sources
Helixi462 – 4643Combined sources
Turni472 – 4743Combined sources
Helixi476 – 50227Combined sources
Turni507 – 5093Combined sources
Beta strandi512 – 5154Combined sources
Turni517 – 5193Combined sources
Beta strandi521 – 5255Combined sources
Helixi527 – 5304Combined sources
Turni531 – 5355Combined sources
Beta strandi540 – 5445Combined sources
Beta strandi549 – 5524Combined sources
Helixi556 – 5638Combined sources
Turni564 – 5674Combined sources
Helixi568 – 58518Combined sources
Helixi586 – 5883Combined sources
Helixi589 – 61325Combined sources
Beta strandi615 – 6173Combined sources
Beta strandi623 – 6253Combined sources
Beta strandi631 – 6377Combined sources
Turni640 – 6445Combined sources
Beta strandi653 – 6586Combined sources
Turni659 – 6613Combined sources
Beta strandi664 – 6685Combined sources
Helixi675 – 69117Combined sources
Beta strandi695 – 7039Combined sources
Beta strandi706 – 7116Combined sources
Helixi724 – 73815Combined sources
Beta strandi744 – 7496Combined sources
Helixi756 – 77217Combined sources
Beta strandi777 – 7837Combined sources
Helixi785 – 7928Combined sources
Beta strandi797 – 80711Combined sources
Beta strandi810 – 82011Combined sources
Helixi827 – 8337Combined sources
Helixi838 – 85013Combined sources
Turni851 – 8555Combined sources
Helixi875 – 89218Combined sources
Helixi896 – 8983Combined sources
Helixi901 – 91717Combined sources
Helixi921 – 9288Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2O8BX-ray2.75A1-934[»]
2O8CX-ray3.37A1-934[»]
2O8DX-ray3.00A1-934[»]
2O8EX-ray3.30A1-934[»]
2O8FX-ray3.25A1-934[»]
3THWX-ray3.09A1-934[»]
3THXX-ray2.70A1-934[»]
3THYX-ray2.89A1-934[»]
3THZX-ray4.30A1-934[»]
ProteinModelPortaliP43246.
SMRiP43246. Positions 1-930.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43246.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni601 – 67171Interaction with EXO1Add
BLAST

Sequence similaritiesi

Belongs to the DNA mismatch repair MutS family.Curated

Phylogenomic databases

eggNOGiCOG0249.
GeneTreeiENSGT00550000074867.
HOGENOMiHOG000196498.
HOVERGENiHBG006399.
InParanoidiP43246.
KOiK08735.
OMAiLNKCRTP.
OrthoDBiEOG76DTRW.
PhylomeDBiP43246.
TreeFamiTF351780.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR011184. 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.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF01624. 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]
PIRSFiPIRSF005813. MSH2. 1 hit.
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P43246-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MAVQPKETLQ LESAAEVGFV RFFQGMPEKP TTTVRLFDRG DFYTAHGEDA
60 70 80 90 100
LLAAREVFKT QGVIKYMGPA GAKNLQSVVL SKMNFESFVK DLLLVRQYRV
110 120 130 140 150
EVYKNRAGNK ASKENDWYLA YKASPGNLSQ FEDILFGNND MSASIGVVGV
160 170 180 190 200
KMSAVDGQRQ VGVGYVDSIQ RKLGLCEFPD NDQFSNLEAL LIQIGPKECV
210 220 230 240 250
LPGGETAGDM GKLRQIIQRG GILITERKKA DFSTKDIYQD LNRLLKGKKG
260 270 280 290 300
EQMNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LTTFDFSQYM
310 320 330 340 350
KLDIAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTPQGQR LVNQWIKQPL
360 370 380 390 400
MDKNRIEERL NLVEAFVEDA ELRQTLQEDL LRRFPDLNRL AKKFQRQAAN
410 420 430 440 450
LQDCYRLYQG INQLPNVIQA LEKHEGKHQK LLLAVFVTPL TDLRSDFSKF
460 470 480 490 500
QEMIETTLDM DQVENHEFLV KPSFDPNLSE LREIMNDLEK KMQSTLISAA
510 520 530 540 550
RDLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS TVDIQKNGVK
560 570 580 590 600
FTNSKLTSLN EEYTKNKTEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA
610 620 630 640 650
QLDAVVSFAH VSNGAPVPYV RPAILEKGQG RIILKASRHA CVEVQDEIAF
660 670 680 690 700
IPNDVYFEKD KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA
710 720 730 740 750
EVSIVDCILA RVGAGDSQLK GVSTFMAEML ETASILRSAT KDSLIIIDEL
760 770 780 790 800
GRGTSTYDGF GLAWAISEYI ATKIGAFCMF ATHFHELTAL ANQIPTVNNL
810 820 830 840 850
HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPKHV IECAKQKALE
860 870 880 890 900
LEEFQYIGES QGYDIMEPAA KKCYLEREQG EKIIQEFLSK VKQMPFTEMS
910 920 930
EENITIKLKQ LKAEVIAKNN SFVNEIISRI KVTT
Length:934
Mass (Da):104,743
Last modified:November 1, 1995 - v1
Checksum:i664A058C78242E05
GO
Isoform 2 (identifier: P43246-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:868
Mass (Da):97,323
Checksum:i1BC5218379005E26
GO

Sequence cautioni

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.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti784 – 7841F → I in BX649122. (PubMed:17974005)Curated
Sequence conflicti836 – 8361F → S in BX649122. (PubMed:17974005)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti2 – 21A → T in HNPCC1. 1 Publication
VAR_054511
Natural varianti8 – 81T → M Could be associated with increased colorectal cancer susceptibility. 3 Publications
Corresponds to variant rs17217716 [ dbSNP | Ensembl ].
VAR_013171
Natural varianti13 – 131S → I in colorectal cancer. 1 Publication
VAR_043736
Natural varianti17 – 171V → F in gastric cancer; unknown pathological significance; cryptic acceptor splice site suppressed on ex vivo splicing assay. 1 Publication
VAR_043737
Natural varianti33 – 331T → P in HNPCC1; shows slightly reduced mismatch binding or release efficiency. 1 Publication
VAR_043738
Natural varianti40 – 401G → S in CRC. 1 Publication
VAR_043739
Natural varianti43 – 431Y → C.1 Publication
Corresponds to variant rs17217723 [ dbSNP | Ensembl ].
VAR_019233
Natural varianti44 – 441T → M in HNPCC1; repair proficient. 1 Publication
VAR_043740
Natural varianti45 – 451A → V in HNPCC1; repair proficient. 1 Publication
VAR_043741
Natural varianti46 – 461H → Q in HNPCC1. 2 Publications
Corresponds to variant rs33946261 [ dbSNP | Ensembl ].
VAR_004470
Natural varianti92 – 921Missing in HNPCC1; unknown pathological significance. 3 Publications
VAR_043742
Natural varianti93 – 931L → F in HNPCC1. 1 Publication
VAR_043743
Natural varianti96 – 961R → H.1 Publication
VAR_004471
Natural varianti98 – 981Y → C in HNPCC1; unknown pathological significance. 1 Publication
VAR_043744
Natural varianti102 – 1021V → I in HNPCC1. 1 Publication
VAR_043745
Natural varianti106 – 1061R → K.1 Publication
Corresponds to variant rs41295286 [ dbSNP | Ensembl ].
VAR_038026
Natural varianti110 – 1101K → T in HNPCC1; somatic mutation. 1 Publication
VAR_043746
Natural varianti127 – 1271N → 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. 2 Publications
Corresponds to variant rs17217772 [ dbSNP | Ensembl ].
VAR_019234
Natural varianti139 – 1391N → S in HNPCC1.
VAR_004472
Natural varianti145 – 1451I → M in HNPCC1; mismatch repair proficient. 1 Publication
Corresponds to variant rs63750124 [ dbSNP | Ensembl ].
VAR_004473
Natural varianti161 – 1611V → D in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. 2 Publications
VAR_012936
Natural varianti162 – 1621G → A in HNPCC1. 1 Publication
VAR_054512
Natural varianti162 – 1621G → 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. 2 Publications
VAR_043747
Natural varianti163 – 1631V → D in HNPCC1. 1 Publication
VAR_043748
Natural varianti163 – 1631V → G in HNPCC1. 1 Publication
VAR_022670
Natural varianti164 – 1641G → R in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. 1 Publication
VAR_043749
Natural varianti165 – 1651Y → D Associated with HNPCC1; unknown pathological significance; repair deficient.
VAR_067284
Natural varianti167 – 1671D → 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. 3 Publications
VAR_004474
Natural varianti169 – 1691I → V in HNPCC1; unknown pathological significance. 2 Publications
Corresponds to variant rs63750716 [ dbSNP | Ensembl ].
VAR_043750
Natural varianti173 – 1731L → P in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. 1 Publication
VAR_043751
Natural varianti175 – 1751L → P in HNPCC1. 1 Publication
VAR_043752
Natural varianti177 – 1771E → H Associated with HNPCC1; requires 2 nucleotide substitutions; unknown pathological significance; repair proficient.
VAR_067285
Natural varianti187 – 1871L → P in HNPCC1; affects protein stability; associated with an absence of the protein in tumors. 1 Publication
VAR_043753
Natural varianti198 – 1981E → G in HNPCC1.
VAR_054513
Natural varianti199 – 1991C → R in glioma; also associated with HNPCC1; has no effect on ex vivo splicing assay. 2 Publications
VAR_012937
Natural varianti203 – 2031G → R in CRC; unknown pathological significance; somatic mutation. 1 Publication
VAR_043754
Natural varianti205 – 2051E → Q Shows no defects; mismatch repair proficient.
VAR_068705
Natural varianti216 – 2161I → V in HNPCC1; unknown pathological significance; shows slightly reduced mismatch binding or release efficiency. 1 Publication
VAR_012938
Natural varianti246 – 2461K → Q in HNPCC1; unknown pathological significance. 1 Publication
VAR_043755
Natural varianti265 – 31450Missing in HNPCC1. 1 Publication
VAR_004475Add
BLAST
Natural varianti272 – 2721A → 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. 2 Publications
Corresponds to variant rs34136999 [ dbSNP | Ensembl ].
VAR_043756
Natural varianti283 – 2831D → Y in HNPCC1. 1 Publication
VAR_043757
Natural varianti305 – 3051A → T in HNPCC1; repair proficient. 1 Publication
VAR_004476
Natural varianti322 – 3221G → 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. 14 Publications