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P43246

- MSH2_HUMAN

UniProt

P43246 - MSH2_HUMAN

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
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    • History
      Entry version 169 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
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    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 binding Source: UniProtKB
    11. protein C-terminus binding Source: UniProtKB
    12. protein homodimerization activity Source: HGNC
    13. protein kinase binding Source: UniProtKB
    14. 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

    Keywords - Biological processi

    DNA damage, DNA repair

    Keywords - Ligandi

    ATP-binding, DNA-binding, Nucleotide-binding

    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

    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.
    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

    ArrayExpressiP43246.
    BgeeiP43246.
    CleanExiHS_MSH2.
    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 – 2411
    Beta strandi33 – 386
    Beta strandi40 – 467
    Helixi48 – 569
    Beta strandi59 – 613
    Beta strandi65 – 717
    Beta strandi75 – 817
    Helixi82 – 9413
    Beta strandi99 – 1057
    Beta strandi117 – 1248
    Helixi129 – 1313
    Helixi132 – 1354
    Beta strandi147 – 1526
    Beta strandi155 – 1584
    Beta strandi160 – 1678
    Turni168 – 1714
    Beta strandi172 – 1798
    Helixi185 – 19410
    Beta strandi197 – 2048
    Helixi208 – 22013
    Beta strandi223 – 2275
    Helixi229 – 2324
    Helixi237 – 2448
    Turni252 – 2543
    Helixi255 – 2573
    Helixi259 – 2624
    Helixi264 – 27714
    Helixi279 – 2813
    Helixi283 – 2853
    Beta strandi289 – 2935
    Helixi296 – 2983
    Helixi304 – 3096
    Helixi326 – 3305
    Helixi336 – 34712
    Helixi353 – 36715
    Helixi370 – 3778
    Turni378 – 3803
    Helixi381 – 3833
    Helixi387 – 3959
    Helixi401 – 41111
    Helixi414 – 42310
    Beta strandi424 – 4263
    Beta strandi427 – 4293
    Helixi432 – 4354
    Helixi437 – 45519
    Helixi462 – 4643
    Turni472 – 4743
    Helixi476 – 50227
    Turni507 – 5093
    Beta strandi512 – 5154
    Turni517 – 5193
    Beta strandi521 – 5255
    Helixi527 – 5304
    Turni531 – 5355
    Beta strandi540 – 5445
    Beta strandi549 – 5524
    Helixi556 – 5638
    Turni564 – 5674
    Helixi568 – 58518
    Helixi586 – 5883
    Helixi589 – 61325
    Beta strandi615 – 6173
    Beta strandi623 – 6253
    Beta strandi631 – 6377
    Turni640 – 6445
    Beta strandi653 – 6586
    Turni659 – 6613
    Beta strandi664 – 6685
    Helixi675 – 69117
    Beta strandi695 – 7039
    Beta strandi706 – 7116
    Helixi724 – 73815
    Beta strandi744 – 7496
    Helixi756 – 77217
    Beta strandi777 – 7837
    Helixi785 – 7928
    Beta strandi797 – 80711
    Beta strandi810 – 82011
    Helixi827 – 8337
    Helixi838 – 85013
    Turni851 – 8555
    Helixi875 – 89218
    Helixi896 – 8983
    Helixi901 – 91717
    Helixi921 – 9288

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    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

    MAVQPKETLQ LESAAEVGFV RFFQGMPEKP TTTVRLFDRG DFYTAHGEDA    50
    LLAAREVFKT QGVIKYMGPA GAKNLQSVVL SKMNFESFVK DLLLVRQYRV 100
    EVYKNRAGNK ASKENDWYLA YKASPGNLSQ FEDILFGNND MSASIGVVGV 150
    KMSAVDGQRQ VGVGYVDSIQ RKLGLCEFPD NDQFSNLEAL LIQIGPKECV 200
    LPGGETAGDM GKLRQIIQRG GILITERKKA DFSTKDIYQD LNRLLKGKKG 250
    EQMNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LTTFDFSQYM 300
    KLDIAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTPQGQR LVNQWIKQPL 350
    MDKNRIEERL NLVEAFVEDA ELRQTLQEDL LRRFPDLNRL AKKFQRQAAN 400
    LQDCYRLYQG INQLPNVIQA LEKHEGKHQK LLLAVFVTPL TDLRSDFSKF 450
    QEMIETTLDM DQVENHEFLV KPSFDPNLSE LREIMNDLEK KMQSTLISAA 500
    RDLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS TVDIQKNGVK 550
    FTNSKLTSLN EEYTKNKTEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA 600
    QLDAVVSFAH VSNGAPVPYV RPAILEKGQG RIILKASRHA CVEVQDEIAF 650
    IPNDVYFEKD KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA 700
    EVSIVDCILA RVGAGDSQLK GVSTFMAEML ETASILRSAT KDSLIIIDEL 750
    GRGTSTYDGF GLAWAISEYI ATKIGAFCMF ATHFHELTAL ANQIPTVNNL 800
    HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPKHV IECAKQKALE 850
    LEEFQYIGES QGYDIMEPAA KKCYLEREQG EKIIQEFLSK VKQMPFTEMS 900
    EENITIKLKQ LKAEVIAKNN SFVNEIISRI KVTT 934
    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.

    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
    Corresponds to variant rs4987188 [ dbSNP | Ensembl ].
    VAR_004477
    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 varianti328 – 3281A → P Shows significantly decreased repair efficiency when associated with variant Ser-127; presumed to enhance cancer risk considerably when associated with variant Ser-127.
    VAR_068706
    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 varianti342 – 3421V → I in colorectal cancer. 1 Publication
    VAR_043762
    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 varianti367 – 3671V → I Shows no defects; mismatch repair proficient.
    VAR_068707
    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 varianti419 – 4191Q → K in CRC; unknown pathological significance; the equivalent substitution in yeast partially affects mismatch repair in vitro. 3 Publications
    Corresponds to variant rs63750006 [ dbSNP | Ensembl ].