| Tbio | DNA mismatch repair protein Msh6 |
Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, 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. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction.
This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
Comments
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Adenocarcinoma of lung | 142 | 0.0 | 0.0 |
| COLORECTAL CANCER, HEREDITARY NONPOLYPOSIS, TYPE 5 | 1 | 0.0 | 0.0 |
| Colorectal Neoplasms, Hereditary Nonpolyposis | 9 | 0.0 | 0.0 |
| Endometrial Neoplasms | 55 | 0.0 | 0.0 |
| Microsatellite Instability | 12 | 0.0 | 0.0 |
| Turcot syndrome | 5 | 0.0 | 0.0 |
| Disease | Target Count | P-value |
|---|---|---|
| non-small cell lung cancer | 2890 | 5.9e-21 |
| juvenile dermatomyositis | 1187 | 1.6e-11 |
| nasopharyngeal carcinoma | 1058 | 1.0e-05 |
| medulloblastoma, large-cell | 6241 | 3.3e-05 |
| group 3 medulloblastoma | 4104 | 4.4e-05 |
| psoriasis | 6694 | 1.1e-04 |
| atypical teratoid / rhabdoid tumor | 5112 | 1.2e-04 |
| lung cancer | 4740 | 2.5e-04 |
| Down syndrome | 499 | 3.1e-04 |
| intraductal papillary-mucinous adenoma (IPMA) | 2955 | 3.5e-04 |
| dermatomyositis | 966 | 3.8e-04 |
| primitive neuroectodermal tumor | 3035 | 1.0e-03 |
| invasive ductal carcinoma | 2951 | 1.2e-03 |
| Multiple myeloma | 1332 | 2.3e-03 |
| pediatric high grade glioma | 1064 | 2.8e-03 |
| Waldenstrons macroglobulinemia | 765 | 1.4e-02 |
| osteosarcoma | 7950 | 2.8e-02 |
| subependymal giant cell astrocytoma | 2287 | 4.0e-02 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Chronic obstructive pulmonary disease | 184 | 0.0 | 2.4 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| ovarian cancer | 8520 | 0.0 | 0.0100752235565464 |
| Disease | log2 FC | p |
|---|---|---|
| ovarian cancer | 1.300 | 1.0e-02 |
| lung cancer | 1.100 | 2.5e-04 |
| ependymoma | 1.600 | 4.9e-07 |
| glioblastoma | 1.400 | 4.0e-04 |
| lung adenocarcinoma | 1.840 | 6.2e-08 |
| atypical teratoid / rhabdoid tumor | 2.100 | 1.2e-04 |
| dermatomyositis | 1.100 | 3.8e-04 |
| Down syndrome | 1.500 | 3.1e-04 |
| group 3 medulloblastoma | 1.800 | 4.4e-05 |
| intraductal papillary-mucinous adenoma (... | -1.300 | 3.5e-04 |
| invasive ductal carcinoma | -1.352 | 1.2e-03 |
| juvenile dermatomyositis | 1.014 | 1.6e-11 |
| medulloblastoma, large-cell | 1.100 | 3.3e-05 |
| Multiple myeloma | 1.507 | 2.3e-03 |
| nasopharyngeal carcinoma | 1.200 | 1.0e-05 |
| non-small cell lung cancer | 1.426 | 5.9e-21 |
| osteosarcoma | 1.217 | 2.8e-02 |
| pediatric high grade glioma | 1.600 | 2.8e-03 |
| primitive neuroectodermal tumor | 1.200 | 1.0e-03 |
| psoriasis | -2.200 | 1.1e-04 |
| subependymal giant cell astrocytoma | -1.232 | 4.0e-02 |
| Waldenstrons macroglobulinemia | 1.395 | 1.4e-02 |
MSRQSTLYSFFPKSPALSDANKASARASREGGRAAAAPGASPSPGGDAAWSEAGPGPRPLARSASPPKAK 1 - 70 NLNGGLRRSVAPAAPTSCDFSPGDLVWAKMEGYPWWPCLVYNHPFDGTFIREKGKSVRVHVQFFDDSPTR 71 - 140 GWVSKRLLKPYTGSKSKEAQKGGHFYSAKPEILRAMQRADEALNKDKIKRLELAVCDEPSEPEEEEEMEV 141 - 210 GTTYVTDKSEEDNEIESEEEVQPKTQGSRRSSRQIKKRRVISDSESDIGGSDVEFKPDTKEEGSSDEISS 211 - 280 GVGDSESEGLNSPVKVARKRKRMVTGNGSLKRKSSRKETPSATKQATSISSETKNTLRAFSAPQNSESQA 281 - 350 HVSGGGDDSSRPTVWYHETLEWLKEEKRRDEHRRRPDHPDFDASTLYVPEDFLNSCTPGMRKWWQIKSQN 351 - 420 FDLVICYKVGKFYELYHMDALIGVSELGLVFMKGNWAHSGFPEIAFGRYSDSLVQKGYKVARVEQTETPE 421 - 490 MMEARCRKMAHISKYDRVVRREICRIITKGTQTYSVLEGDPSENYSKYLLSLKEKEEDSSGHTRAYGVCF 491 - 560 VDTSLGKFFIGQFSDDRHCSRFRTLVAHYPPVQVLFEKGNLSKETKTILKSSLSCSLQEGLIPGSQFWDA 561 - 630 SKTLRTLLEEEYFREKLSDGIGVMLPQVLKGMTSESDSIGLTPGEKSELALSALGGCVFYLKKCLIDQEL 631 - 700 LSMANFEEYIPLDSDTVSTTRSGAIFTKAYQRMVLDAVTLNNLEIFLNGTNGSTEGTLLERVDTCHTPFG 701 - 770 KRLLKQWLCAPLCNHYAINDRLDAIEDLMVVPDKISEVVELLKKLPDLERLLSKIHNVGSPLKSQNHPDS 771 - 840 RAIMYEETTYSKKKIIDFLSALEGFKVMCKIIGIMEEVADGFKSKILKQVISLQTKNPEGRFPDLTVELN 841 - 910 RWDTAFDHEKARKTGLITPKAGFDSDYDQALADIRENEQSLLEYLEKQRNRIGCRTIVYWGIGRNRYQLE 911 - 980 IPENFTTRNLPEEYELKSTKKGCKRYWTKTIEKKLANLINAEERRDVSLKDCMRRLFYNFDKNYKDWQSA 981 - 1050 VECIAVLDVLLCLANYSRGGDGPMCRPVILLPEDTPPFLELKGSRHPCITKTFFGDDFIPNDILIGCEEE 1051 - 1120 EQENGKAYCVLVTGPNMGGKSTLMRQAGLLAVMAQMGCYVPAEVCRLTPIDRVFTRLGASDRIMSGESTF 1121 - 1190 FVELSETASILMHATAHSLVLVDELGRGTATFDGTAIANAVVKELAETIKCRTLFSTHYHSLVEDYSQNV 1191 - 1260 AVRLGHMACMVENECEDPSQETITFLYKFIKGACPKSYGFNAARLANLPEEVIQKGHRKAREFEKMNQSL 1261 - 1330 RLFREVCLASERSTVDAEAVHKLLTLIKEL 1331 - 1360 //
