MSH6
entrez
2956
canonical
uniprot
P52701
canonical
ensembl
ENSG00000116062
resolver
ensp
ENSP00000234420
resolver
ensp
ENSP00000390382
resolver
ensp
ENSP00000397484
resolver
ensp
ENSP00000406248
resolver
ensp
ENSP00000446475
resolver
ensp
ENSP00000498629
resolver
ensp
ENSP00000501310
resolver
ensp
ENSP00000514749
resolver
ensp
ENSP00000565746
resolver
ensp
ENSP00000565748
resolver
ensp
ENSP00000606568
resolver
ensp
ENSP00000690716
resolver
ensp
ENSP00000786628
resolver
ensp
ENSP00000793273
resolver
enst
ENST00000411819
resolver
enst
ENST00000420813
resolver
enst
ENST00000455383
resolver
enst
ENST00000652107
resolver
enst
ENST00000673637
resolver
enst
ENST00000700000
resolver
genesymbol
MSH6
resolver
genesymbol_syn
GTBP
resolver
hgnc
HGNC:7329
resolver
uniprot
A0A494C0M1
resolver
uniprot
A0A8V8TPJ4
resolver
uniprot
B4DF41
resolver
uniprot
B4E3I4
resolver
uniprot
C9J7Y7
resolver
uniprot
C9J8Y8
resolver
uniprot
C9JH55
resolver
uniprot
F5H2F9
resolver
uniprot
O43706
resolver
uniprot
O43917
resolver
uniprot
Q3SWU9
resolver
uniprot
Q8TCX4
resolver
uniprot
Q9BTB5
resolver
uniprot_entry
A0A494C0M1_HUMAN
resolver
uniprot_entry
A0A8V8TPJ4_HUMAN
resolver
uniprot_entry
MSH6_HUMAN
resolver
uniprot_entry
Q3SWU9_HUMAN
resolver
uniprot_sec
B4DF41
resolver
uniprot_sec
B4E3I4
resolver
uniprot_sec
C9J7Y7
resolver
uniprot_sec
C9J8Y8
resolver
uniprot_sec
C9JH55
resolver
uniprot_sec
F5H2F9
resolver
uniprot_sec
O43706
resolver
uniprot_sec
O43917
resolver
uniprot_sec
Q8TCX4
resolver
uniprot_sec
Q9BTB5
resolver
amino_acid_sequence
MSRQSTLYSFFPKSPALSDANKASARASREGGRAAAAPGASPSPGGDAAWSEAGPGPRPLARSASPPKAKNLNGGLRRSVAPAAPTSCDFSPGDLVWAKMEGYPWWPCLVYNHPFDGTFIREKGKSVRVHVQFFDDSPTRGWVSKRLLKPYTGSKSKEAQKGGHFYSAKPEILRAMQRADEALNKDKIKRLELAVCDEPSEPEEEEEMEVGTTYVTDKSEEDNEIESEEEVQPKTQGSRRSSRQIKKRRVISDSESDIGGSDVEFKPDTKEEGSSDEISSGVGDSESEGLNSPVKVARKRKRMVTGNGSLKRKSSRKETPSATKQATSISSETKNTLRAFSAPQNSESQAHVSGGGDDSSRPTVWYHETLEWLKEEKRRDEHRRRPDHPDFDASTLYVPEDFLNSCTPGMRKWWQIKSQNFDLVICYKVGKFYELYHMDALIGVSELGLVFMKGNWAHSGFPEIAFGRYSDSLVQKGYKVARVEQTETPEMMEARCRKMAHISKYDRVVRREICRIITKGTQTYSVLEGDPSENYSKYLLSLKEKEEDSSGHTRAYGVCFVDTSLGKFFIGQFSDDRHCSRFRTLVAHYPPVQVLFEKGNLSKETKTILKSSLSCSLQEGLIPGSQFWDASKTLRTLLEEEYFREKLSDGIGVMLPQVLKGMTSESDSIGLTPGEKSELALSALGGCVFYLKKCLIDQELLSMANFEEYIPLDSDTVSTTRSGAIFTKAYQRMVLDAVTLNNLEIFLNGTNGSTEGTLLERVDTCHTPFGKRLLKQWLCAPLCNHYAINDRLDAIEDLMVVPDKISEVVELLKKLPDLERLLSKIHNVGSPLKSQNHPDSRAIMYEETTYSKKKIIDFLSALEGFKVMCKIIGIMEEVADGFKSKILKQVISLQTKNPEGRFPDLTVELNRWDTAFDHEKARKTGLITPKAGFDSDYDQALADIRENEQSLLEYLEKQRNRIGCRTIVYWGIGRNRYQLEIPENFTTRNLPEEYELKSTKKGCKRYWTKTIEKKLANLINAEERRDVSLKDCMRRLFYNFDKNYKDWQSAVECIAVLDVLLCLANYSRGGDGPMCRPVILLPEDTPPFLELKGSRHPCITKTFFGDDFIPNDILIGCEEEEQENGKAYCVLVTGPNMGGKSTLMRQAGLLAVMAQMGCYVPAEVCRLTPIDRVFTRLGASDRIMSGESTFFVELSETASILMHATAHSLVLVDELGRGTATFDGTAIANAVVKELAETIKCRTLFSTHYHSLVEDYSQNVAVRLGHMACMVENECEDPSQETITFLYKFIKGACPKSYGFNAARLANLPEEVIQKGHRKAREFEKMNQSLRLFREVCLASERSTVDAEAVHKLLTLIKEL
uniprot
proteins
disease_involvement
DISEASE: Lynch syndrome 5 (LYNCH5) [MIM:614350]: A form of Lynch syndrome, 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. Lynch syndrome is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, it 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 Lynch syndrome 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 Lynch syndrome' or 'incomplete Lynch syndrome' 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. {ECO:0000269|PubMed:10480359, ECO:0000269|PubMed:10521294, ECO:0000269|PubMed:11586295, ECO:0000269|PubMed:12658575, ECO:0000269|PubMed:14974087, ECO:0000269|PubMed:15365995, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22102614, ECO:0000269|PubMed:9354786}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:11153917, ECO:0000269|PubMed:14961575}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Mismatch repair cancer syndrome 3 (MMRCS3) [MIM:619097]: An autosomal recessive form of mismatch repair cancer syndrome, a childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. {ECO:0000269|PubMed:17557300}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:10413423, ECO:0000269|PubMed:10537275, ECO:0000269|PubMed:10699937, ECO:0000269|PubMed:11153917, ECO:0000269|PubMed:11470537, ECO:0000269|PubMed:11709755, ECO:0000269|PubMed:11807791, ECO:0000269|PubMed:12522549, ECO:0000269|PubMed:14520694, ECO:0000269|PubMed:14961575, ECO:0000269|PubMed:15483016, ECO:0000269|PubMed:22102614}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: 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. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679, ECO:0000269|PubMed:9822680}.
uniprot
proteins
mass_dalton
152786
uniprot
proteins
mutagenesis
MUTAGEN 103; /note="Y->A: Abolishes binding to H3K36me3 and DNA mismatch repair activity."; /evidence="ECO:0000269|PubMed:23622243"; MUTAGEN 105..106; /note="WW->AA: Abolishes binding to H3K36me3 and DNA mismatch repair activity."; /evidence="ECO:0000269|PubMed:23622243"; MUTAGEN 1140; /note="K->R: No effect on mismatch binding, complete loss of DNA repair function when associated with MSH2 mutant R-675."; /evidence="ECO:0000269|PubMed:9564049
uniprot
proteins
post_translational_modification
PTM: The N-terminus is blocked.; PTM: Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway. {ECO:0000269|PubMed:15808853}.
uniprot
proteins
protein_family
DNA mismatch repair MutS family
uniprot
proteins
pubmed
10078208
uniprot
proteins
pubmed
10413423
uniprot
proteins
pubmed
10480359
uniprot
proteins
pubmed
10521294
uniprot
proteins
pubmed
10537275
uniprot
proteins
pubmed
10660545
uniprot
proteins
pubmed
10699937
uniprot
proteins
pubmed
10783165
uniprot
proteins
pubmed
11153917
uniprot
proteins
pubmed
11470537
uniprot
proteins
pubmed
11586295
uniprot
proteins
pubmed
11709755
uniprot
proteins
pubmed
11807791
uniprot
proteins
pubmed
12522549
uniprot
proteins
pubmed
12658575
uniprot
proteins
pubmed
14520694
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14961575
uniprot
proteins
pubmed
14974087
uniprot
proteins
pubmed
15064730
uniprot
proteins
pubmed
15354210
uniprot
proteins
pubmed
15365995
uniprot
proteins
pubmed
15483016
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15808853
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17531815
uniprot
proteins
pubmed
17557300
uniprot
proteins
pubmed
18033691
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21120944
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21957315
uniprot
proteins
pubmed
22102614
uniprot
proteins
pubmed
22581703
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23622243
uniprot
proteins
pubmed
26300262
uniprot
proteins
pubmed
7604264
uniprot
proteins
pubmed
7604265
uniprot
proteins
pubmed
7604266
uniprot
proteins
pubmed
8838326
uniprot
proteins
pubmed
8942985
uniprot
proteins
pubmed
9354786
uniprot
proteins
pubmed
9455487
uniprot
proteins
pubmed
9564049
uniprot
proteins
pubmed
9822679
uniprot
proteins
pubmed
9822680
uniprot
proteins
pubmed
9889267
uniprot
proteins
sequence_length
1360
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23622243}. Chromosome {ECO:0000269|PubMed:23622243}. Note=Associates with H3K36me3 via its PWWP domain.
uniprot
proteins