Reactome | UniProt:P52701 MSH6

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UniProt:P52701 MSH6 Show undefined attributes

chain	chain:1-1360
checksum	4A4AA9F8ECB8FFE9
comment	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.SUBUNIT Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Heterodimer consisting of MSH2-MSH6 (MutS alpha) (PubMed:7604264, PubMed:8942985). Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with MCM9 (PubMed:26300262). 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 (PubMed:10783165). This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains (PubMed:10783165).SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 protein UL12.INTERACTION Associates with H3K36me3 via its PWWP domain.ALTERNATIVE PRODUCTS The PWWP domain specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3).PTM The N-terminus is blocked.PTM Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.SIMILARITY Belongs to the DNA mismatch repair MutS family.
crossReference	[DatabaseIdentifier:12357033] RefSeq:NP_001393743.1 [DatabaseIdentifier:12357027] RefSeq:NP_001393738.1 [DatabaseIdentifier:12357028] RefSeq:NP_001393725.1 [DatabaseIdentifier:12357029] RefSeq:NP_001393745.1 [DatabaseIdentifier:12357023] RefSeq:NP_000170.1 [DatabaseIdentifier:11467938] ENSEMBL:ENSG00000116062 [DatabaseIdentifier:11563919] ENSEMBL:ENSP00000446475 [DatabaseIdentifier:11563920] ENSEMBL:ENSP00000234420 [DatabaseIdentifier:11686618] ENSEMBL:ENST00000234420 [DatabaseIdentifier:11686619] ENSEMBL:ENST00000540021 [DatabaseIdentifier:11784852] GeneCards:MSH6 [DatabaseIdentifier:11800387] GlyGen:P52701 [DatabaseIdentifier:11837943] HPA:ENSG00000116062-MSH6 [DatabaseIdentifier:12122443] OpenTargets:ENSG00000116062 [DatabaseIdentifier:12137148] Orphanet:MSH6 [DatabaseIdentifier:12162021] PDB:2O8C [DatabaseIdentifier:12162014] PDB:2O8B [DatabaseIdentifier:12162016] PDB:2GFU [DatabaseIdentifier:12162020] PDB:2O8D [DatabaseIdentifier:12162019] PDB:2O8E [DatabaseIdentifier:12162018] PDB:6OQM [DatabaseIdentifier:12162017] PDB:2O8F [DatabaseIdentifier:12162015] PDB:8AG6 [DatabaseIdentifier:12260993] PRO:P52701 [DatabaseIdentifier:12282764] Pharos - Targets:P52701 [DatabaseIdentifier:12357032] RefSeq:NP_001268422.1 [DatabaseIdentifier:12357030] RefSeq:NP_001268421.1 [DatabaseIdentifier:12357035] RefSeq:NP_001393758.1 [DatabaseIdentifier:12357024] RefSeq:NP_001393741.1 [DatabaseIdentifier:12357025] RefSeq:NP_001393752.1 [DatabaseIdentifier:12357026] RefSeq:NP_001393740.1 [DatabaseIdentifier:12357034] RefSeq:NP_001268423.1 [DatabaseIdentifier:12357031] RefSeq:NP_001393744.1
databaseName	UniProt
dbId	59591
description	recommendedName: fullName evidence="1"DNA mismatch repair protein Msh6 shortName evidence="48"hMSH6 alternativeName: fullName evidence="47"G/T mismatch-binding protein shortName evidence="49"GTBP shortName evidence="1"GTMBP alternativeName: fullName evidence="51"MutS protein homolog 6 alternativeName: MutS-alpha 160 kDa subunit shortName evidence="46"p160
displayName	UniProt:P52701 MSH6
geneName	MSH6 GTBP
identifier	P52701
isSequenceChanged	false
keyword	3D-structure Acetylation Alternative splicing ATP-binding Chromosome Direct protein sequencing Disease variant DNA damage DNA repair DNA-binding Hereditary nonpolyposis colorectal cancer Host-virus interaction Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome
modified	[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	MSH6
otherIdentifier	1017_at 11749000_a_at 11755368_a_at 1569034_PM_a_at 1569034_a_at 16879916 16879923 17122192 2003_s_at 202911_PM_at 202911_at 211449_PM_at 211449_at 211450_PM_s_at 211450_s_at 240148_PM_at 240148_at 2481143 2481147 2481148 2481149 2481151 2481153 2481155 2481156 2481157 2481159 2481160 2481161 2481162 2481163 2481164 2481165 2481166 2481167 2481168 2481169 2481170 2481171 2481172 2481173 2481174 2481175 2481176 2481177 2481178 2481179 2481180 2481184 2481186 2481188 2956 68631_at 80342_at 8041888 A_14_P103048 A_14_P124635 A_14_P129086 A_14_P201209 A_21_P0011802 A_21_P0012003 A_23_P102202 GE60542 GO:0000166 GO:0000287 GO:0000400 GO:0000710 GO:0000785 GO:0002376 GO:0003677 GO:0003682 GO:0003684 GO:0003690 GO:0003824 GO:0005515 GO:0005524 GO:0005634 GO:0005654 GO:0005694 GO:0005794 GO:0005829 GO:0006281 GO:0006298 GO:0006310 GO:0006325 GO:0006974 GO:0007283 GO:0008094 GO:0008340 GO:0008630 GO:0009411 GO:0016446 GO:0016447 GO:0019899 GO:0022414 GO:0030983 GO:0032137 GO:0032142 GO:0032143 GO:0032301 GO:0032357 GO:0032405 GO:0043531 GO:0045190 GO:0045910 GO:0051053 GO:0097193 GO:0140003 GO:0140097 GO:0140657 GO:0140664 HMNXSV003001487 HMNXSV003013728 HMNXSV003056463 Hs.232119.0.A1_3p_at Hs2.196970.2.S1_3p_a_at ILMN_1729051 ILMN_1731085 PH_hs_0018833 PH_hs_0026021 TC02000297.hg TC02000299.hg TC02003220.hg U73737_at g2687868_3p_a_at g2687868_3p_at g4504190_3p_at p9784
physicalEntity	[EntityWithAccessionedSequence:R-HSA-5357528] MSH6 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5632954] MSH6 L222* [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000116062] ENSEMBL:ENSG00000116062 MSH6 [ReferenceDNASequence:12735835] UCSC:P52701 MSH6 [ReferenceDNASequence:11332632] BioGPS Gene:2956 MSH6 [ReferenceDNASequence:11399046] COSMIC - genes:MSH6 MSH6 [ReferenceDNASequence:11409013] CTD Gene:2956 MSH6 [ReferenceDNASequence:11435962] dbSNP Gene:2956 MSH6 [ReferenceDNASequence:11816477] HGNC:7329 MSH6 [ReferenceDNASequence:11874258] KEGG:hsa:2956 MSH6 [ReferenceDNASequence:11962421] Monarch:2956 MSH6 [ReferenceDNASequence:12046514] NCBI Gene:2956 MSH6 [ReferenceDNASequence:12108053] OMIM:600678 MSH6
referenceTranscript	[ReferenceRNASequence:12538864] RefSeq:NM_000179.3 MSH6 [ReferenceRNASequence:12538871] RefSeq:NM_001406816.1 MSH6 [ReferenceRNASequence:12538869] RefSeq:NM_001406812.1 MSH6 [ReferenceRNASequence:12538867] RefSeq:NM_001406811.1 MSH6 [ReferenceRNASequence:12538873] RefSeq:NM_001406814.1 MSH6 [ReferenceRNASequence:12538863] RefSeq:NM_001281492.2 MSH6 [ReferenceRNASequence:12538865] RefSeq:NM_001281494.2 MSH6 [ReferenceRNASequence:12538874] RefSeq:NM_001406809.1 MSH6 [ReferenceRNASequence:12538870] RefSeq:NM_001406815.1 MSH6 [ReferenceRNASequence:12538866] RefSeq:NM_001281493.2 MSH6 [ReferenceRNASequence:12538872] RefSeq:NM_001406796.1 MSH6 [ReferenceRNASequence:12538868] RefSeq:NM_001406823.1 MSH6 [ReferenceRNASequence:12538875] RefSeq:NM_001406829.1 MSH6
schemaClass	ReferenceGeneProduct
secondaryIdentifier	MSH6_HUMAN B4DF41 B4E3I4 F5H2F9 O43706 O43917 Q8TCX4 Q9BTB5
sequenceLength	1360
species	[Species:48887] Homo sapiens
stId	uniprot:P52701
url	http://purl.uniprot.org/uniprot/P52701

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-5357528] MSH6 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-5632954] MSH6 L222* [nucleoplasm]
(referenceSequence)	[NonsenseMutation:5632985] Nonsense mutation at L-leucine 222
(interactor)	[UndirectedInteraction:11208105] UniProt:P01106 <-> UniProt:P52701 (IntAct) [UndirectedInteraction:11287317] UniProt:P12004 <-> UniProt:P52701 (IntAct) [UndirectedInteraction:11289917] UniProt:P43246 <-> UniProt:P52701 (IntAct) [UndirectedInteraction:11304495] UniProt:P52701 <-> UniProt:Q9NXL9 (IntAct) [UndirectedInteraction:11304497] UniProt:P52701 <-> UniProt:P01112 (IntAct) [UndirectedInteraction:11304499] UniProt:P52701 <-> IntAct:EBI-1187714 (IntAct)