Q03834 · MSH6_YEAST
- ProteinDNA mismatch repair protein MSH6
- GeneMSH6
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1242 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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. MSH6 provides substrate-binding and substrate specificity to the complex. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs. Acts mainly to repair base-base and single insertion-deletion mismatches that occur during replication, but can also repair longer insertion-deletion loops (IDLs), although with decreasing efficiency as the size of the extrahelical loop increases. 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 by the MutS alpha complex is crucial for MMR. Both subunits bind ATP, but with differing affinities, and their ATPase kinetics are also very different. MSH6 binds and hydrolyzes ATP rapidly, whereas MSH2 catalyzes ATP at a substantially slower rate. Binding to a mismatched base pair suppresses MSH6-catalyzed ATP hydrolysis, but not the activity of MSH2. ATP binding to both subunits is necessary to trigger a change in MutS alpha interaction with mismatched DNA, converting MutS alpha into a sliding clamp capable of hydrolysis-independent movement along DNA, and also facilitates formation of ternary complexes containing MutS and MutL proteins and the mismatch. May also be involved in resolution of recombination intermediates.
Miscellaneous
Present with 5330 molecules/cell in log phase SD medium.
Activity regulation
Inhibited by Cd2+.
Features
Showing features for dna binding, binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | MutSalpha complex | |
Cellular Component | nucleus | |
Molecular Function | ATP binding | |
Molecular Function | ATP hydrolysis activity | |
Molecular Function | ATP-dependent DNA damage sensor activity | |
Molecular Function | four-way junction DNA binding | |
Molecular Function | mismatched DNA binding | |
Molecular Function | nucleic acid binding | |
Biological Process | interstrand cross-link repair | |
Biological Process | meiotic mismatch repair | |
Biological Process | mismatch repair | |
Biological Process | replication fork arrest |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA mismatch repair protein MSH6
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Saccharomycetaceae > Saccharomyces
Accessions
- Primary accessionQ03834
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 26-27 | Partially functional in a mismatch repair assay; when associated with 33-AA-34. | ||||
Sequence: KQ → AA | ||||||
Mutagenesis | 33-34 | Abolishes interaction with PCNA (POL30), but only causes a moderate mismatch repair defect. Partially functional in a mismatch repair assay; when associated with 26-AA-27. | ||||
Sequence: FF → AA | ||||||
Mutagenesis | 301 | Fully functional in a mismatch repair assay. | ||||
Sequence: L → V | ||||||
Mutagenesis | 313 | Fully functional in a mismatch repair assay. | ||||
Sequence: P → A | ||||||
Mutagenesis | 337 | Shows defects in both homoduplex and mispair DNA binding and is only partially functional in a mismatch repair assay. | ||||
Sequence: F → A | ||||||
Mutagenesis | 337 | Partially functional in a mismatch repair assay. | ||||
Sequence: F → H, I, or Y | ||||||
Mutagenesis | 337 | Completely abolishes mismatch repair. | ||||
Sequence: F → K | ||||||
Mutagenesis | 337 | In MSH6-6; partially functional in a mismatch repair assay. | ||||
Sequence: F → S | ||||||
Mutagenesis | 339 | Defective in repairing 8-oxo-G-A mismatches. | ||||
Sequence: E → A | ||||||
Mutagenesis | 340-343 | In MSH6-340; shows defects in mispair DNA binding, but not in homoduplex DNA binding. | ||||
Sequence: LYEK → CFAE | ||||||
Mutagenesis | 368 | Moderately reduced activity in a mismatch repair assay. | ||||
Sequence: G → A | ||||||
Mutagenesis | 370 | Partially functional in a mismatch repair assay. | ||||
Sequence: P → A | ||||||
Mutagenesis | 393 | Moderately reduced activity in a mismatch repair assay. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 393 | In MSH6-5; partially functional in a mismatch repair assay. | ||||
Sequence: Q → R | ||||||
Mutagenesis | 412 | Completely abolishes mismatch repair. | ||||
Sequence: R → A | ||||||
Mutagenesis | 412 | In MSH6-7; partially functional in a mismatch repair assay. | ||||
Sequence: R → G | ||||||
Mutagenesis | 421 | In PMS3-1; completely abolishes mismatch repair. | ||||
Sequence: G → D | ||||||
Mutagenesis | 477 | Partially functional in a mismatch repair assay. | ||||
Sequence: G → R | ||||||
Mutagenesis | 848 | Fully functional in a mismatch repair assay. | ||||
Sequence: K → A | ||||||
Mutagenesis | 852 | Moderately reduced activity in a mismatch repair assay. | ||||
Sequence: R → A | ||||||
Mutagenesis | 987 | Has no defect in mismatch DNA binding, but lacks ATP-induced conformational change. | ||||
Sequence: G → D | ||||||
Mutagenesis | 988 | Impairs ATP binding; reduces catalytic activity 13-fold for ATP hydrolysis. | ||||
Sequence: K → A | ||||||
Mutagenesis | 1036 | In MSH6-4; defective for ATP-induced sliding clamp formation and assembly of ternary complexes with MutL alpha. | ||||
Sequence: S → P | ||||||
Mutagenesis | 1062 | Reduces catalytic activity 13-fold for ATP hydrolysis. | ||||
Sequence: E → A | ||||||
Mutagenesis | 1067 | In MSH6-3; defective for ATP-induced sliding clamp formation and assembly of ternary complexes with MutL alpha. | ||||
Sequence: G → D | ||||||
Mutagenesis | 1096 | In MSH6-9; shows normal mispair binding and dissociation, but fails to show complete mispair activation of the ATPase. | ||||
Sequence: H → A | ||||||
Mutagenesis | 1142 | In MSH6-2; defective for ATP-induced sliding clamp formation, but assembles ternary complexes with MutL alpha. | ||||
Sequence: G → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 38 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000115213 | 1-1242 | DNA mismatch repair protein MSH6 | |||
Sequence: MAPATPKTSKTAHFENGSTSSQKKMKQSSLLSFFSKQVPSGTPSKKVQKPTPATLENTATDKITKNPQGGKTGKLFVDVDEDNDLTIAEETVSTVRSDIMHSQEPQSDTMLNSNTTEPKSTTTDEDLSSSQSRRNHKRRVNYAESDDDDSDTTFTAKRKKGKVVDSESDEDEYLPDKNDGDEDDDIADDKEDIKGELAEDSGDDDDLISLAETTSKKKFSYNTSHSSSPFTRNISRDNSKKKSRPNQAPSRSYNPSHSQPSATSKSSKFNKQNEERYQWLVDERDAQRRPKSDPEYDPRTLYIPSSAWNKFTPFEKQYWEIKSKMWDCIVFFKKGKFFELYEKDALLANALFDLKIAGGGRANMQLAGIPEMSFEYWAAQFIQMGYKVAKVDQRESMLAKEMREGSKGIVKRELQCILTSGTLTDGDMLHSDLATFCLAIREEPGNFYNETQLDSSTIVQKLNTKIFGAAFIDTATGELQMLEFEDDSECTKLDTLMSQVRPMEVVMERNNLSTLANKIVKFNSAPNAIFNEVKAGEEFYDCDKTYAEIISSEYFSTEEDWPEVLKSYYDTGKKVGFSAFGGLLYYLKWLKLDKNLISMKNIKEYDFVKSQHSMVLDGITLQNLEIFSNSFDGSDKGTLFKLFNRAITPMGKRMMKKWLMHPLLRKNDIESRLDSVDSLLQDITLREQLEITFSKLPDLERMLARIHSRTIKVKDFEKVITAFETIIELQDSLKNNDLKGDVSKYISSFPEGLVEAVKSWTNAFERQKAINENIIVPQRGFDIEFDKSMDRIQELEDELMEILMTYRKQFKCSNIQYKDSGKEIYTIEIPISATKNVPSNWVQMAANKTYKRYYSDEVRALARSMAEAKEIHKTLEEDLKNRLCQKFDAHYNTIWMPTIQAISNIDCLLAITRTSEYLGAPSCRPTIVDEVDSKTNTQLNGFLKFKSLRHPCFNLGATTAKDFIPNDIELGKEQPRLGLLTGANAAGKSTILRMACIAVIMAQMGCYVPCESAVLTPIDRIMTRLGANDNIMQGKSTFFVELAETKKILDMATNRSLLVVDELGRGGSSSDGFAIAESVLHHVATHIQSLGFFATHYGTLASSFKHHPQVRPLKMSILVDEATRNVTFLYKMLEGQSEGSFGMHVASMCGISKEIIDNAQIAADNLEHTSRLVKERDLAANNLNGEVVSVPGGLQSDFVRIAYGDGLKNTKLGSGEGVLNYDWNIKRNVLKSLFSIIDDLQS | ||||||
Modified residue | 102 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 145 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 150 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 201 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 451 | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms a ternary complex with MutL alpha (MLH1-PMS1). MutS alpha interacts with proliferating cell nuclear antigen (PCNA/POL30). This interaction is disrupted upon binding of MutS alpha to mismatch DNA.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q03834 | MSH2 P25847 | 7 | EBI-11383, EBI-11352 | |
BINARY | Q03834 | POL30 P15873 | 5 | EBI-11383, EBI-12993 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-271 | Disordered | ||||
Sequence: MAPATPKTSKTAHFENGSTSSQKKMKQSSLLSFFSKQVPSGTPSKKVQKPTPATLENTATDKITKNPQGGKTGKLFVDVDEDNDLTIAEETVSTVRSDIMHSQEPQSDTMLNSNTTEPKSTTTDEDLSSSQSRRNHKRRVNYAESDDDDSDTTFTAKRKKGKVVDSESDEDEYLPDKNDGDEDDDIADDKEDIKGELAEDSGDDDDLISLAETTSKKKFSYNTSHSSSPFTRNISRDNSKKKSRPNQAPSRSYNPSHSQPSATSKSSKFNK | ||||||
Compositional bias | 9-67 | Polar residues | ||||
Sequence: SKTAHFENGSTSSQKKMKQSSLLSFFSKQVPSGTPSKKVQKPTPATLENTATDKITKNP | ||||||
Motif | 27-34 | PIP box | ||||
Sequence: QSSLLSFF | ||||||
Compositional bias | 88-128 | Polar residues | ||||
Sequence: AEETVSTVRSDIMHSQEPQSDTMLNSNTTEPKSTTTDEDLS | ||||||
Compositional bias | 129-168 | Basic and acidic residues | ||||
Sequence: SSQSRRNHKRRVNYAESDDDDSDTTFTAKRKKGKVVDSES | ||||||
Compositional bias | 169-190 | Acidic residues | ||||
Sequence: DEDEYLPDKNDGDEDDDIADDK | ||||||
Compositional bias | 213-234 | Polar residues | ||||
Sequence: TTSKKKFSYNTSHSSSPFTRNI | ||||||
Compositional bias | 245-268 | Polar residues | ||||
Sequence: PNQAPSRSYNPSHSQPSATSKSSK | ||||||
Region | 305-421 | Mispair-binding domain | ||||
Sequence: SSAWNKFTPFEKQYWEIKSKMWDCIVFFKKGKFFELYEKDALLANALFDLKIAGGGRANMQLAGIPEMSFEYWAAQFIQMGYKVAKVDQRESMLAKEMREGSKGIVKRELQCILTSG |
Domain
The PIP box serves as a PCNA(POL30)-recognition and -binding motif.
Sequence similarities
Belongs to the DNA mismatch repair MutS family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,242
- Mass (Da)140,080
- Last updated1996-11-01 v1
- Checksum11A6883AADCFA222
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 9-67 | Polar residues | ||||
Sequence: SKTAHFENGSTSSQKKMKQSSLLSFFSKQVPSGTPSKKVQKPTPATLENTATDKITKNP | ||||||
Compositional bias | 88-128 | Polar residues | ||||
Sequence: AEETVSTVRSDIMHSQEPQSDTMLNSNTTEPKSTTTDEDLS | ||||||
Compositional bias | 129-168 | Basic and acidic residues | ||||
Sequence: SSQSRRNHKRRVNYAESDDDDSDTTFTAKRKKGKVVDSES | ||||||
Compositional bias | 169-190 | Acidic residues | ||||
Sequence: DEDEYLPDKNDGDEDDDIADDK | ||||||
Compositional bias | 213-234 | Polar residues | ||||
Sequence: TTSKKKFSYNTSHSSSPFTRNI | ||||||
Compositional bias | 245-268 | Polar residues | ||||
Sequence: PNQAPSRSYNPSHSQPSATSKSSK |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Z47746 EMBL· GenBank· DDBJ | CAA87671.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BK006938 EMBL· GenBank· DDBJ | DAA11942.1 EMBL· GenBank· DDBJ | Genomic DNA |