Homo sapiens L. (human) [HSA]

FULL NAME: DNA mismatch repair protein Msh6


DESCRIPTION:
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.

STRUCTURE SIMILARITY:
Contains 1 PWWP domain.
Belongs to the DNA mismatch repair mutS family.


POST-TRANSLATIONAL MODIFICATION:
Phosphorylated upon DNA damage, probably by ATM or ATR.
Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway.
The N-terminus is blocked.


RELATED PATHWAY(S):
mismatch repair (MMR)


RELATED DISEASE(S):
mismatch repair cancer syndrome (MMRCS)
COLORECTAL CANCER
hereditary non-polyposis colorectal cancer, TYPE 5
endometrial cancer


Amino acids sequence

        10         20         30         40         50         60
MSRQSTLYSF FPKSPALSDA NKASARASRE GGRAAAAPGA SPSPGGDAAW SEAGPGPRPL
        70         80         90        100        110        120
ARSASPPKAK NLNGGLRRSV APAAPTSCDF SPGDLVWAKM EGYPWWPCLV YNHPFDGTFI
       130        140        150        160        170        180
REKGKSVRVH VQFFDDSPTR GWVSKRLLKP YTGSKSKEAQ KGGHFYSAKP EILRAMQRAD
       190        200        210        220        230        240
EALNKDKIKR LELAVCDEPS EPEEEEEMEV GTTYVTDKSE EDNEIESEEE VQPKTQGSRR
       250        260        270        280        290        300
SSRQIKKRRV ISDSESDIGG SDVEFKPDTK EEGSSDEISS GVGDSESEGL NSPVKVARKR
       310        320        330        340        350        360
KRMVTGNGSL KRKSSRKETP SATKQATSIS SETKNTLRAF SAPQNSESQA HVSGGGDDSS
       370        380        390        400        410        420
RPTVWYHETL EWLKEEKRRD EHRRRPDHPD FDASTLYVPE DFLNSCTPGM RKWWQIKSQN
       430        440        450        460        470        480
FDLVICYKVG KFYELYHMDA LIGVSELGLV FMKGNWAHSG FPEIAFGRYS DSLVQKGYKV
       490        500        510        520        530        540
ARVEQTETPE MMEARCRKMA HISKYDRVVR REICRIITKG TQTYSVLEGD PSENYSKYLL
       550        560        570        580        590        600
SLKEKEEDSS GHTRAYGVCF VDTSLGKFFI GQFSDDRHCS RFRTLVAHYP PVQVLFEKGN
       610        620        630        640        650        660
LSKETKTILK SSLSCSLQEG LIPGSQFWDA SKTLRTLLEE EYFREKLSDG IGVMLPQVLK
       670        680        690        700        710        720
GMTSESDSIG LTPGEKSELA LSALGGCVFY LKKCLIDQEL LSMANFEEYI PLDSDTVSTT
       730        740        750        760        770        780
RSGAIFTKAY QRMVLDAVTL NNLEIFLNGT NGSTEGTLLE RVDTCHTPFG KRLLKQWLCA
       790        800        810        820        830        840
PLCNHYAIND RLDAIEDLMV VPDKISEVVE LLKKLPDLER LLSKIHNVGS PLKSQNHPDS
       850        860        870        880        890        900
RAIMYEETTY SKKKIIDFLS ALEGFKVMCK IIGIMEEVAD GFKSKILKQV ISLQTKNPEG
       910        920        930        940        950        960
RFPDLTVELN RWDTAFDHEK ARKTGLITPK AGFDSDYDQA LADIRENEQS LLEYLEKQRN
       970        980        990       1000       1010       1020
RIGCRTIVYW GIGRNRYQLE IPENFTTRNL PEEYELKSTK KGCKRYWTKT IEKKLANLIN
      1030       1040       1050       1060       1070       1080
AEERRDVSLK DCMRRLFYNF DKNYKDWQSA VECIAVLDVL LCLANYSRGG DGPMCRPVIL
      1090       1100       1110       1120       1130       1140
LPEDTPPFLE LKGSRHPCIT KTFFGDDFIP NDILIGCEEE EQENGKAYCV LVTGPNMGGK
      1150       1160       1170       1180       1190       1200
STLMRQAGLL AVMAQMGCYV PAEVCRLTPI DRVFTRLGAS DRIMSGESTF FVELSETASI
      1210       1220       1230       1240       1250       1260
LMHATAHSLV LVDELGRGTA TFDGTAIANA VVKELAETIK CRTLFSTHYH SLVEDYSQNV
      1270       1280       1290       1300       1310       1320
AVRLGHMACM VENECEDPSQ ETITFLYKFI KGACPKSYGF NAARLANLPE EVIQKGHRKA
      1330       1340       1350       1360
REFEKMNQSL RLFREVCLAS ERSTVDAEAV HKLLTLIKEL  

Encoded by MSH6 gene

FULL NAME: mutS homolog 6 (E. coli)


OTHER NAME(S):
GTBP
HNPCC5
HSAP


DESCRIPTION:
This gene encodes a protein similar to the MutS protein. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides, prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein of this gene combines with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene have been identified in individuals with hereditary nonpolyposis colon cancer (HNPCC) and endometrial cancer. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atgtcgcgac agagcaccct gtacagcttc ttccccaagt ctccggcgct gagtgatgcc
        70         80         90        100        110        120
aacaaggcct cggccagggc ctcacgcgaa ggcggccgtg ccgccgctgc ccccggggcc
       130        140        150        160        170        180
tctccttccc caggcgggga tgcggcctgg agcgaggctg ggcctgggcc caggcccttg
       190        200        210        220        230        240
gcgcgctccg cgtcaccgcc caaggcgaag aacctcaacg gagggctgcg gagatcggta
       250        260        270        280        290        300
gcgcctgctg cccccaccag ttgtgacttc tcaccaggag atttggtttg ggccaagatg
       310        320        330        340        350        360
gagggttacc cctggtggcc ttgtctggtt tacaaccacc cctttgatgg aacattcatc
       370        380        390        400        410        420
cgcgagaaag ggaaatcagt ccgtgttcat gtacagtttt ttgatgacag cccaacaagg
       430        440        450        460        470        480
ggctgggtta gcaaaaggct tttaaagcca tatacaggtt caaaatcaaa ggaagcccag
       490        500        510        520        530        540
aagggaggtc atttttacag tgcaaagcct gaaatactga gagcaatgca acgtgcagat
       550        560        570        580        590        600
gaagccttaa ataaagacaa gattaagagg cttgaattgg cagtttgtga tgagccctca
       610        620        630        640        650        660
gagccagaag aggaagaaga gatggaggta ggcacaactt acgtaacaga taagagtgaa
       670        680        690        700        710        720
gaagataatg aaattgagag tgaagaggaa gtacagccta agacacaagg atctaggcga
       730        740        750        760        770        780
agtagccgcc aaataaaaaa acgaagggtc atatcagatt ctgagagtga cattggtggc
       790        800        810        820        830        840
tctgatgtgg aatttaagcc agacactaag gaggaaggaa gcagtgatga aataagcagt
       850        860        870        880        890        900
ggagtggggg atagtgagag tgaaggcctg aacagccctg tcaaagttgc tcgaaagcgg
       910        920        930        940        950        960
aagagaatgg tgactggaaa tggctctctt aaaaggaaaa gctctaggaa ggaaacgccc
       970        980        990       1000       1010       1020
tcagccacca aacaagcaac tagcatttca tcagaaacca agaatacttt gagagctttc
      1030       1040       1050       1060       1070       1080
tctgcccctc aaaattctga atcccaagcc cacgttagtg gaggtggtga tgacagtagt
      1090       1100       1110       1120       1130       1140
cgccctactg tttggtatca tgaaacttta gaatggctta aggaggaaaa gagaagagat
      1150       1160       1170       1180       1190       1200
gagcacagga ggaggcctga tcaccccgat tttgatgcat ctacactcta tgtgcctgag
      1210       1220       1230       1240       1250       1260
gatttcctca attcttgtac tcctgggatg aggaagtggt ggcagattaa gtctcagaac
      1270       1280       1290       1300       1310       1320
tttgatcttg tcatctgtta caaggtgggg aaattttatg agctgtacca catggatgct
      1330       1340       1350       1360       1370       1380
cttattggag tcagtgaact ggggctggta ttcatgaaag gcaactgggc ccattctggc
      1390       1400       1410       1420       1430       1440
tttcctgaaa ttgcatttgg ccgttattca gattccctgg tgcagaaggg ctataaagta
      1450       1460       1470       1480       1490       1500
gcacgagtgg aacagactga gactccagaa atgatggagg cacgatgtag aaagatggca
      1510       1520       1530       1540       1550       1560
catatatcca agtatgatag agtggtgagg agggagatct gtaggatcat taccaagggt
      1570       1580       1590       1600       1610       1620
acacagactt acagtgtgct ggaaggtgat ccctctgaga actacagtaa gtatcttctt
      1630       1640       1650       1660       1670       1680
agcctcaaag aaaaagagga agattcttct ggccatactc gtgcatatgg tgtgtgcttt
      1690       1700       1710       1720       1730       1740
gttgatactt cactgggaaa gtttttcata ggtcagtttt cagatgatcg ccattgttcg
      1750       1760       1770       1780       1790       1800
agatttagga ctctagtggc acactatccc ccagtacaag ttttatttga aaaaggaaat
      1810       1820       1830       1840       1850       1860
ctctcaaagg aaactaaaac aattctaaag agttcattgt cctgttctct tcaggaaggt
      1870       1880       1890       1900       1910       1920
ctgatacccg gctcccagtt ttgggatgca tccaaaactt tgagaactct ccttgaggaa
      1930       1940       1950       1960       1970       1980
gaatatttta gggaaaagct aagtgatggc attggggtga tgttacccca ggtgcttaaa
      1990       2000       2010       2020       2030       2040
ggtatgactt cagagtctga ttccattggg ttgacaccag gagagaaaag tgaattggcc
      2050       2060       2070       2080       2090       2100
ctctctgctc taggtggttg tgtcttctac ctcaaaaaat gccttattga tcaggagctt
      2110       2120       2130       2140       2150       2160
ttatcaatgg ctaattttga agaatatatt cccttggatt ctgacacagt cagcactaca
      2170       2180       2190       2200       2210       2220
agatctggtg ctatcttcac caaagcctat caacgaatgg tgctagatgc agtgacatta
      2230       2240       2250       2260       2270       2280
aacaacttgg agatttttct gaatggaaca aatggttcta ctgaaggaac cctactagag
      2290       2300       2310       2320       2330       2340
agggttgata cttgccatac tccttttggt aagcggctcc taaagcaatg gctttgtgcc
      2350       2360       2370       2380       2390       2400
ccactctgta accattatgc tattaatgat cgtctagatg ccatagaaga cctcatggtt
      2410       2420       2430       2440       2450       2460
gtgcctgaca aaatctccga agttgtagag cttctaaaga agcttccaga tcttgagagg
      2470       2480       2490       2500       2510       2520
ctactcagta aaattcataa tgttgggtct cccctgaaga gtcagaacca cccagacagc
      2530       2540       2550       2560       2570       2580
agggctataa tgtatgaaga aactacatac agcaagaaga agattattga ttttctttct
      2590       2600       2610       2620       2630       2640
gctctggaag gattcaaagt aatgtgtaaa attataggga tcatggaaga agttgctgat
      2650       2660       2670       2680       2690       2700
ggttttaagt ctaaaatcct taagcaggtc atctctctgc agacaaaaaa tcctgaaggt
      2710       2720       2730       2740       2750       2760
cgttttcctg atttgactgt agaattgaac cgatgggata cagcctttga ccatgaaaag
      2770       2780       2790       2800       2810       2820
gctcgaaaga ctggacttat tactcccaaa gcaggctttg actctgatta tgaccaagct
      2830       2840       2850       2860       2870       2880
cttgctgaca taagagaaaa tgaacagagc ctcctggaat acctagagaa acagcgcaac
      2890       2900       2910       2920       2930       2940
agaattggct gtaggaccat agtctattgg gggattggta ggaaccgtta ccagctggaa
      2950       2960       2970       2980       2990       3000
attcctgaga atttcaccac tcgcaatttg ccagaagaat acgagttgaa atctaccaag
      3010       3020       3030       3040       3050       3060
aagggctgta aacgatactg gaccaaaact attgaaaaga agttggctaa tctcataaat
      3070       3080       3090       3100       3110       3120
gctgaagaac ggagggatgt atcattgaag gactgcatgc ggcgactgtt ctataacttt
      3130       3140       3150       3160       3170       3180
gataaaaatt acaaggactg gcagtctgct gtagagtgta tcgcagtgtt ggatgtttta
      3190       3200       3210       3220       3230       3240
ctgtgcctgg ctaactatag tcgagggggt gatggtccta tgtgtcgccc agtaattctg
      3250       3260       3270       3280       3290       3300
ttgccggaag ataccccccc cttcttagag cttaaaggat cacgccatcc ttgcattacg
      3310       3320       3330       3340       3350       3360
aagacttttt ttggagatga ttttattcct aatgacattc taataggctg tgaggaagag
      3370       3380       3390       3400       3410       3420
gagcaggaaa atggcaaagc ctattgtgtg cttgttactg gaccaaatat ggggggcaag
      3430       3440       3450       3460       3470       3480
tctacgctta tgagacaggc tggcttatta gctgtaatgg cccagatggg ttgttacgtc
      3490       3500       3510       3520       3530       3540
cctgctgaag tgtgcaggct cacaccaatt gatagagtgt ttactagact tggtgcctca
      3550       3560       3570       3580       3590       3600
gacagaataa tgtcaggtga aagtacattt tttgttgaat taagtgaaac tgccagcata
      3610       3620       3630       3640       3650       3660
ctcatgcatg caacagcaca ttctctggtg cttgtggatg aattaggaag aggtactgca
      3670       3680       3690       3700       3710       3720
acatttgatg ggacggcaat agcaaatgca gttgttaaag aacttgctga gactataaaa
      3730       3740       3750       3760       3770       3780
tgtcgtacat tattttcaac tcactaccat tcattagtag aagattattc tcaaaatgtt
      3790       3800       3810       3820       3830       3840
gctgtgcgcc taggacatat ggcatgcatg gtagaaaatg aatgtgaaga ccccagccag
      3850       3860       3870       3880       3890       3900
gagactatta cgttcctcta taaattcatt aagggagctt gtcctaaaag ctatggcttt
      3910       3920       3930       3940       3950       3960
aatgcagcaa ggcttgctaa tctcccagag gaagttattc aaaagggaca tagaaaagca
      3970       3980       3990       4000       4010       4020
agagaatttg agaagatgaa tcagtcacta cgattatttc gggaagtttg cctggctagt
      4030       4040       4050       4060       4070       4080
gaaaggtcaa ctgtagatgc tgaagctgtc cataaattgc tgactttgat taaggaatta

tag     

Last modification date: Oct. 2, 2011