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P54276

- MSH6_MOUSE

UniProt

P54276 - MSH6_MOUSE

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Protein

DNA mismatch repair protein Msh6

Gene

Msh6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1132 – 11398ATPSequence Analysis

GO - Molecular functioni

  1. ADP binding Source: Ensembl
  2. ATP binding Source: UniProtKB-KW
  3. chromatin binding Source: MGI
  4. damaged DNA binding Source: MGI
  5. DNA binding Source: MGI
  6. DNA-dependent ATPase activity Source: RefGenome
  7. four-way junction DNA binding Source: RefGenome
  8. guanine/thymine mispair binding Source: MGI
  9. magnesium ion binding Source: Ensembl
  10. methylated histone binding Source: UniProtKB
  11. mismatched DNA binding Source: UniProtKB
  12. oxidized purine DNA binding Source: Ensembl
  13. single base insertion or deletion binding Source: RefGenome
  14. single guanine insertion binding Source: Ensembl
  15. single thymine insertion binding Source: Ensembl

GO - Biological processi

  1. ATP catabolic process Source: GOC
  2. determination of adult lifespan Source: MGI
  3. intrinsic apoptotic signaling pathway Source: MGI
  4. intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  5. isotype switching Source: MGI
  6. maintenance of DNA repeat elements Source: RefGenome
  7. meiotic mismatch repair Source: RefGenome
  8. mismatch repair Source: MGI
  9. negative regulation of DNA recombination Source: MGI
  10. positive regulation of helicase activity Source: Ensembl
  11. reciprocal meiotic recombination Source: RefGenome
  12. response to UV Source: MGI
  13. somatic hypermutation of immunoglobulin genes Source: MGI
  14. somatic recombination of immunoglobulin gene segments Source: MGI
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
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 namesi
Name:Msh6
Synonyms:Gtmbp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 17

Organism-specific databases

MGIiMGI:1343961. Msh6.

Subcellular locationi

Nucleus By similarity. Chromosome By similarity
Note: Associates with H3K36me3 via its PWWP domain.By similarity

GO - Cellular componenti

  1. Golgi apparatus Source: Ensembl
  2. MutSalpha complex Source: MGI
  3. nuclear chromatin Source: MGI
  4. plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13581358DNA mismatch repair protein Msh6PRO_0000115208Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei14 – 141PhosphoserineBy similarity
Modified residuei38 – 381PhosphoserineBy similarity
Modified residuei40 – 401PhosphoserineBy similarity
Modified residuei67 – 671N6-acetyllysineBy similarity
Modified residuei91 – 911PhosphoserineBy similarity
Modified residuei137 – 1371PhosphoserineBy similarity
Modified residuei200 – 2001PhosphoserineBy similarity
Modified residuei219 – 2191PhosphoserineBy similarity
Modified residuei227 – 2271PhosphoserineBy similarity
Modified residuei252 – 2521PhosphoserineBy similarity
Modified residuei254 – 2541PhosphoserineBy similarity
Modified residuei256 – 2561PhosphoserineBy similarity
Modified residuei261 – 2611Phosphoserine1 Publication
Modified residuei269 – 2691PhosphothreonineBy similarity
Modified residuei274 – 2741PhosphoserineBy similarity
Modified residuei275 – 2751PhosphoserineBy similarity
Modified residuei279 – 2791PhosphoserineBy similarity
Modified residuei280 – 2801PhosphoserineBy similarity
Modified residuei503 – 5031N6-acetyllysineBy similarity
Modified residuei827 – 8271PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP54276.
PaxDbiP54276.
PRIDEiP54276.

PTM databases

PhosphoSiteiP54276.

Expressioni

Gene expression databases

BgeeiP54276.
CleanExiMM_MSH6.
ExpressionAtlasiP54276. baseline and differential.
GenevestigatoriP54276.

Interactioni

Subunit structurei

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.By similarity

Protein-protein interaction databases

BioGridi201528. 5 interactions.
IntActiP54276. 5 interactions.

Structurei

3D structure databases

ProteinModelPortaliP54276.
SMRiP54276. Positions 65-201, 361-1333.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini92 – 15463PWWPPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi201 – 2099Poly-Glu

Domaini

The PWWP domain specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3).By similarity

Sequence similaritiesi

Belongs to the DNA mismatch repair MutS family.Curated
Contains 1 PWWP domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0249.
GeneTreeiENSGT00550000075024.
HOGENOMiHOG000243127.
HOVERGENiHBG000101.
InParanoidiP54276.
KOiK08737.
OMAiALKDCMR.
OrthoDBiEOG7K9K27.
TreeFamiTF105842.

Family and domain databases

Gene3Di3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR017261. 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]
PANTHERiPTHR11361:SF31. PTHR11361:SF31. 1 hit.
PfamiPF01624. 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]
PIRSFiPIRSF037677. DNA_mis_repair_Msh6. 1 hit.
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
SM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF55271. SSF55271. 1 hit.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
PS50812. PWWP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P54276-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSRQSTLYSF FPKSPALGDT KKAAAEASRQ GAAASGASAS RGGDAAWSEA
60 70 80 90 100
EPGSRSAAVS ASSPEAKDLN GGLRRASSSA QAVPPSSCDF SPGDLVWAKM
110 120 130 140 150
EGYPWWPCLV YNHPFDGTFI RKKGKSVRVH VQFFDDSPTR GWVSKRMLKP
160 170 180 190 200
YTGSKSKEAQ KGGHFYSSKS EILRAMQRAD EALSKDTAER LQLAVCDEPS
210 220 230 240 250
EPEEEEETEV HEAYLSDKSE EDNYNESEEE AQPSVQGPRR SSRQVKKRRV
260 270 280 290 300
ISDSESDIGG SDVEFKPDTK QEGSSDDASS GVGDSDSEDL GTFGKGAPKR
310 320 330 340 350
KRAMVAQGGL RRKSLKKETG SAKRATPILS ETKSTLSAFS APQNSESQTH
360 370 380 390 400
VSGGGNDSSG PTVWYHETLE WLKPEKRRDE HRRRPDHPEF NPTTLYVPEE
410 420 430 440 450
FLNSCTPGMR KWWQLKSQNF DLVIFYKVGK FYELYHMDAV IGVSELGLIF
460 470 480 490 500
MKGNWAHSGF PEIAFGRFSD SLVQKGYKVA RVEQTETPEM MEARCRKMAH
510 520 530 540 550
VSKFDRVVRR EICRIITKGT QTYSVLDGDP SENYSRYLLS LKEKEEETSG
560 570 580 590 600
HTRVYGVCFV DTSLGKFFIG QFSDDRHCSR FRTLVAHYPP VQILFEKGNL
610 620 630 640 650
STETKTVLKG SLSSCLQEGL IPGSQFWDAT KTLRTLLEGG YFTGNGDSST
660 670 680 690 700
VLPLVLKGMT SESDSVGLTP GEESELALSA LGGIVFYLKK CLIDQELLSM
710 720 730 740 750
ANFEEYFPLD SDTVSTVKPG AVFTKASQRM VLDAVTLNNL EIFLNGTNGS
760 770 780 790 800
TEGTLLERLD TCHTPFGKRL LKQWLCAPLC SPSAISDRLD AVEDLMAVPD
810 820 830 840 850
KVTEVADLLK KLPDLERLLS KIHNVGSPLK SQNHPDSRAI MYEETTYSKK
860 870 880 890 900
KIIDFLSALE GFKVMCKVSG LLEEVAGGFT SKTLKQVVTL QSKSPKGRFP
910 920 930 940 950
DLTAELQRWD TAFDHEKARK TGLITPKAGF DSDYDQALAD IRENEQSLLE
960 970 980 990 1000
YLDKQRSRLG CKSIVYWGIG RNRYQLEIPE NFATRNLPEE YELKSTKKGC
1010 1020 1030 1040 1050
KRYWTKTIEK KLANLINAEE RRDTSLKDCM RRLFCNFDKN HKDWQSAVEC
1060 1070 1080 1090 1100
IAVLDVLLCL ANYSQGGDGP MCRPEIVLPG EDTHPFLEFK GSRHPCITKT
1110 1120 1130 1140 1150
FFGDDFIPND ILIGCEEEAE EHGKAYCVLV TGPNMGGKST LIRQAGLLAV
1160 1170 1180 1190 1200
MAQLGCYVPA EKCRLTPVDR VFTRLGASDR IMSGESTFFV ELSETASILR
1210 1220 1230 1240 1250
HATAHSLVLV DELGRGTATF DGTAIANAVV KELAETIKCR TLFSTHYHSL
1260 1270 1280 1290 1300
VEDYSKSVCV RLGHMACMVE NECEDPSQET ITFLYKFIKG ACPKSYGFNA
1310 1320 1330 1340 1350
ARLANLPEEV IQKGHRKARE FERMNQSLQL FREVCLATEK PTINGEAIHR

LLALINGL
Length:1,358
Mass (Da):151,084
Last modified:July 27, 2011 - v3
Checksum:i979D289BC69E6047
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti65 – 662EA → DG in AAC53034. (PubMed:8812455)Curated
Sequence conflicti374 – 3752PE → QK in AAC53034. (PubMed:8812455)Curated
Sequence conflicti754 – 7541T → N in AAC53034. (PubMed:8812455)Curated
Sequence conflicti800 – 8001D → Y in AAC53034. (PubMed:8812455)Curated
Sequence conflicti1227 – 12271N → S in AAC53034. (PubMed:8812455)Curated
Sequence conflicti1329 – 13291Q → R in AAC53034. (PubMed:8812455)Curated
Sequence conflicti1333 – 13331E → G in AAC53034. (PubMed:8812455)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS29021.1.
RefSeqiNP_034960.1. NM_010830.2.
UniGeneiMm.18210.

Genome annotation databases

EnsembliENSMUST00000005503; ENSMUSP00000005503; ENSMUSG00000005370.
GeneIDi17688.
KEGGimmu:17688.
UCSCiuc008dvd.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS29021.1.
RefSeqi NP_034960.1. NM_010830.2.
UniGenei Mm.18210.

3D structure databases

ProteinModelPortali P54276.
SMRi P54276. Positions 65-201, 361-1333.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 201528. 5 interactions.
IntActi P54276. 5 interactions.

PTM databases

PhosphoSitei P54276.

Proteomic databases

MaxQBi P54276.
PaxDbi P54276.
PRIDEi P54276.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000005503 ; ENSMUSP00000005503 ; ENSMUSG00000005370 .
GeneIDi 17688.
KEGGi mmu:17688.
UCSCi uc008dvd.2. mouse.

Organism-specific databases

CTDi 2956.
MGIi MGI:1343961. Msh6.

Phylogenomic databases

eggNOGi COG0249.
GeneTreei ENSGT00550000075024.
HOGENOMi HOG000243127.
HOVERGENi HBG000101.
InParanoidi P54276.
KOi K08737.
OMAi ALKDCMR.
OrthoDBi EOG7K9K27.
TreeFami TF105842.

Miscellaneous databases

ChiTaRSi MSH6. mouse.
NextBioi 292264.
PROi P54276.
SOURCEi Search...

Gene expression databases

Bgeei P54276.
CleanExi MM_MSH6.
ExpressionAtlasi P54276. baseline and differential.
Genevestigatori P54276.

Family and domain databases

Gene3Di 3.40.1170.10. 1 hit.
3.40.50.300. 1 hit.
InterProi 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 ]
PANTHERi PTHR11361:SF31. PTHR11361:SF31. 1 hit.
Pfami 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 ]
PIRSFi PIRSF037677. DNA_mis_repair_Msh6. 1 hit.
SMARTi SM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
SM00293. PWWP. 1 hit.
[Graphical view ]
SUPFAMi SSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF55271. SSF55271. 1 hit.
PROSITEi PS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
PS50812. PWWP. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiMSH6_MOUSE
AccessioniPrimary (citable) accession number: P54276
Secondary accession number(s): O54710, Q6GTK8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 109 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3