DNA mismatch repair protein Msh6 - Mus musculus (Mouse)

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P54276 (MSH6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified November 13, 2013. Version 100. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
DNA mismatch repair protein Msh6

Alternative name(s):
G/T mismatch-binding protein
Short name=GTBP
Short name=GTMBP
MutS-alpha 160 kDa subunit
p160

Gene names

Name:	Msh6
Synonyms:	Gtmbp

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1358 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity.
Subunit structure	Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms 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 By similarity.
Subcellular location	Nucleus By similarity. Chromosome By similarity. Note: Associates with H3K36me3 via its PWWP domain By similarity.
Domain	The PWWP domain specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3) By similarity.
Post-translational modification	Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway By similarity.
Sequence similarities	Belongs to the DNA mismatch repair MutS family. Contains 1 PWWP domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Chromosome Nucleus
Ligand	ATP-binding DNA-binding Nucleotide-binding
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	determination of adult lifespan Inferred from mutant phenotype PubMed 10545954 Ref.2. Source: MGI intrinsic apoptotic signaling pathway in response to DNA damage Inferred from mutant phenotype PubMed 15324697. Source: MGI isotype switching Inferred from mutant phenotype PubMed 16618598. Source: MGI maintenance of DNA repeat elements Inferred from Biological aspect of Ancestor. Source: RefGenome meiotic mismatch repair Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of DNA recombination Inferred from mutant phenotype PubMed 10545954. Source: MGI positive regulation of helicase activity Inferred from electronic annotation. Source: Ensembl reciprocal meiotic recombination Inferred from Biological aspect of Ancestor. Source: RefGenome response to UV Inferred from mutant phenotype PubMed 14632208. Source: MGI somatic hypermutation of immunoglobulin genes Inferred from mutant phenotype PubMed 10662804 PubMed 15238604 PubMed 16618598. Source: MGI
Cellular_component	MutSalpha complex Inferred from direct assay PubMed 16713580. Source: MGI nuclear chromatin Inferred from direct assay PubMed 16618598. Source: MGI
Molecular_function	ADP binding Inferred from electronic annotation. Source: Ensembl ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA-dependent ATPase activity Inferred from Biological aspect of Ancestor. Source: RefGenome chromatin binding Inferred from direct assay PubMed 16618598. Source: MGI damaged DNA binding Inferred from mutant phenotype PubMed 10545954. Source: MGI four-way junction DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome guanine/thymine mispair binding Inferred from direct assay PubMed 15324697. Source: MGI magnesium ion binding Inferred from electronic annotation. Source: Ensembl methylated histone residue binding Inferred from sequence or structural similarity. Source: UniProtKB oxidized purine DNA binding Inferred from electronic annotation. Source: Ensembl single base insertion or deletion binding Inferred from Biological aspect of Ancestor. Source: RefGenome single guanine insertion binding Inferred from electronic annotation. Source: Ensembl single thymine insertion binding Inferred from electronic annotation. Source: Ensembl
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1358

1358

DNA mismatch repair protein Msh6

PRO_0000115208

Regions

Domain

92 – 154

PWWP

Nucleotide binding

1132 – 1139

ATP Potential

Compositional bias

201 – 209

Poly-Glu

Amino acid modifications

Modified residue

Phosphoserine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

N6-acetyllysine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

137

Phosphoserine By similarity

Modified residue

200

Phosphoserine By similarity

Modified residue

219

Phosphoserine By similarity

Modified residue

227

Phosphoserine By similarity

Modified residue

252

Phosphoserine By similarity

Modified residue

254

Phosphoserine By similarity

Modified residue

256

Phosphoserine By similarity

Modified residue

261

Phosphoserine Ref.5

Modified residue

269

Phosphothreonine By similarity

Modified residue

274

Phosphoserine By similarity

Modified residue

275

Phosphoserine By similarity

Modified residue

279

Phosphoserine By similarity

Modified residue

280

Phosphoserine By similarity

Modified residue

503

N6-acetyllysine By similarity

Modified residue

827

Phosphoserine By similarity

Experimental info

Sequence conflict

65 – 66

EA → DG in AAC53034. Ref.1

Sequence conflict

374 – 375

PE → QK in AAC53034. Ref.1

Sequence conflict

754

T → N in AAC53034. Ref.1

Sequence conflict

800

D → Y in AAC53034. Ref.1

Sequence conflict

1227

N → S in AAC53034. Ref.1

Sequence conflict

1329

Q → R in AAC53034. Ref.1

Sequence conflict

1333

E → G in AAC53034. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

P54276 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 979D289BC69E6047
Show »

FASTA

1,358

151,084

        10         20         30         40         50         60 
MSRQSTLYSF FPKSPALGDT KKAAAEASRQ GAAASGASAS RGGDAAWSEA EPGSRSAAVS 

        70         80         90        100        110        120 
ASSPEAKDLN GGLRRASSSA QAVPPSSCDF SPGDLVWAKM EGYPWWPCLV YNHPFDGTFI 

       130        140        150        160        170        180 
RKKGKSVRVH VQFFDDSPTR GWVSKRMLKP YTGSKSKEAQ KGGHFYSSKS EILRAMQRAD 

       190        200        210        220        230        240 
EALSKDTAER LQLAVCDEPS EPEEEEETEV HEAYLSDKSE EDNYNESEEE AQPSVQGPRR 

       250        260        270        280        290        300 
SSRQVKKRRV ISDSESDIGG SDVEFKPDTK QEGSSDDASS GVGDSDSEDL GTFGKGAPKR 

       310        320        330        340        350        360 
KRAMVAQGGL RRKSLKKETG SAKRATPILS ETKSTLSAFS APQNSESQTH VSGGGNDSSG 

       370        380        390        400        410        420 
PTVWYHETLE WLKPEKRRDE HRRRPDHPEF NPTTLYVPEE FLNSCTPGMR KWWQLKSQNF 

       430        440        450        460        470        480 
DLVIFYKVGK FYELYHMDAV IGVSELGLIF MKGNWAHSGF PEIAFGRFSD SLVQKGYKVA 

       490        500        510        520        530        540 
RVEQTETPEM MEARCRKMAH VSKFDRVVRR EICRIITKGT QTYSVLDGDP SENYSRYLLS 

       550        560        570        580        590        600 
LKEKEEETSG HTRVYGVCFV DTSLGKFFIG QFSDDRHCSR FRTLVAHYPP VQILFEKGNL 

       610        620        630        640        650        660 
STETKTVLKG SLSSCLQEGL IPGSQFWDAT KTLRTLLEGG YFTGNGDSST VLPLVLKGMT 

       670        680        690        700        710        720 
SESDSVGLTP GEESELALSA LGGIVFYLKK CLIDQELLSM ANFEEYFPLD SDTVSTVKPG 

       730        740        750        760        770        780 
AVFTKASQRM VLDAVTLNNL EIFLNGTNGS TEGTLLERLD TCHTPFGKRL LKQWLCAPLC 

       790        800        810        820        830        840 
SPSAISDRLD AVEDLMAVPD KVTEVADLLK KLPDLERLLS KIHNVGSPLK SQNHPDSRAI 

       850        860        870        880        890        900 
MYEETTYSKK KIIDFLSALE GFKVMCKVSG LLEEVAGGFT SKTLKQVVTL QSKSPKGRFP 

       910        920        930        940        950        960 
DLTAELQRWD TAFDHEKARK TGLITPKAGF DSDYDQALAD IRENEQSLLE YLDKQRSRLG 

       970        980        990       1000       1010       1020 
CKSIVYWGIG RNRYQLEIPE NFATRNLPEE YELKSTKKGC KRYWTKTIEK KLANLINAEE 

      1030       1040       1050       1060       1070       1080 
RRDTSLKDCM RRLFCNFDKN HKDWQSAVEC IAVLDVLLCL ANYSQGGDGP MCRPEIVLPG 

      1090       1100       1110       1120       1130       1140 
EDTHPFLEFK GSRHPCITKT FFGDDFIPND ILIGCEEEAE EHGKAYCVLV TGPNMGGKST 

      1150       1160       1170       1180       1190       1200 
LIRQAGLLAV MAQLGCYVPA EKCRLTPVDR VFTRLGASDR IMSGESTFFV ELSETASILR 

      1210       1220       1230       1240       1250       1260 
HATAHSLVLV DELGRGTATF DGTAIANAVV KELAETIKCR TLFSTHYHSL VEDYSKSVCV 

      1270       1280       1290       1300       1310       1320 
RLGHMACMVE NECEDPSQET ITFLYKFIKG ACPKSYGFNA ARLANLPEEV IQKGHRKARE 

      1330       1340       1350 
FERMNQSLQL FREVCLATEK PTINGEAIHR LLALINGL

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA sequence, map, and expression of the murine homolog of GTBP, a DNA mismatch repair gene." Corradi A., Croci L., Stayton C.L., Gulisano M., Boncinelli E., Consalez G.G. Genomics 36:288-295(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Mutation in the mismatch repair gene Msh6 causes cancer susceptibility." Edelmann W., Yang K., Umar A., Heyer J., Lau K., Fan K., Liedtke W., Cohen P., Kane M.K., Lipford J.R., Yu N., Crouse G.F., Pollard J.W., Kunkel T., Lipkin M., Kolodner R., Kucherlapati R. Cell 91:467-477(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/Ola.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary tumor.
[4]	Donohue P.J., Feng S.L.Y., Alberts G.F., Guo Y., Peifley K.A., Hsu D.K.W., Winkles J.A. Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 375-425 AND 1001-1050.
[5]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U42190 mRNA. Translation: AAC53034.1. AF031087, AF031085, AF031086 Genomic DNA. Translation: AAB88445.1. BC051160 mRNA. Translation: AAH51160.1. BC051634 mRNA. Translation: AAH51634.1. U61388 mRNA. Translation: AAB39930.1. U61389 mRNA. Translation: AAB39931.1.
IPI	IPI00323790.
RefSeq	NP_034960.1. NM_010830.2.
UniGene	Mm.18210.
3D structure databases
ProteinModelPortal	P54276.
SMR	P54276. Positions 65-201, 361-1333.
ModBase	Search...
Protein-protein interaction databases
IntAct	P54276. 4 interactions.
PTM databases
PhosphoSite	P54276.
Proteomic databases
PaxDb	P54276.
PRIDE	P54276.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000005503; ENSMUSP00000005503; ENSMUSG00000005370.
GeneID	17688.
KEGG	mmu:17688.
UCSC	uc008dvd.2. mouse.
Organism-specific databases
CTD	2956.
MGI	MGI:1343961. Msh6.
Phylogenomic databases
eggNOG	COG0249.
GeneTree	ENSGT00550000075024.
HOGENOM	HOG000243127.
HOVERGEN	HBG000101.
InParanoid	Q6GTK8.
KO	K08737.
OMA	HMDAVIG.
OrthoDB	EOG7K9K27.
Gene expression databases
ArrayExpress	P54276.
Bgee	P54276.
CleanEx	MM_MSH6.
Genevestigator	P54276.
Family and domain databases
Gene3D	3.40.1170.10. 1 hit.
InterPro	IPR017261. DNA_mismatch_repair_Msh6. IPR015536. DNA_mismatch_repair_MSH6_C. 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. IPR016151. DNA_mismatch_repair_MutS_N. IPR007860. DNA_mmatch_repair_MutS_con_dom. IPR027417. P-loop_NTPase. IPR000313. PWWP_dom. [Graphical view]
PANTHER	PTHR11361:SF31. PTHR11361:SF31. 1 hit.
Pfam	PF01624. MutS_I. 1 hit. PF05188. MutS_II. 1 hit. PF05192. MutS_III. 1 hit. PF05190. MutS_IV. 1 hit. PF00488. MutS_V. 1 hit. PF00855. PWWP. 1 hit. [Graphical view]
PIRSF	PIRSF037677. DNA_mis_repair_Msh6. 1 hit.
SMART	SM00534. MUTSac. 1 hit. SM00533. MUTSd. 1 hit. SM00293. PWWP. 1 hit. [Graphical view]
SUPFAM	SSF48334. SSF48334. 1 hit. SSF52540. SSF52540. 1 hit. SSF55271. SSF55271. 1 hit.
PROSITE	PS00486. DNA_MISMATCH_REPAIR_2. 1 hit. PS50812. PWWP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MSH6. mouse.
NextBio	292264.
PRO	P54276.
SOURCE	Search...

Entry information

Entry name

MSH6_MOUSE

Accession

Primary (citable) accession number: P54276
Secondary accession number(s): O54710, Q6GTK8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 27, 2011
Last modified:	November 13, 2013
This is version 100 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents