Saccharomyces cerevisiae Meyen ex E.C. Hansen (budding yeast) [SCE]

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. 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.


STRUCTURE SIMILARITY:
Belongs to the DNA mismatch repair mutS family.


ENZYME REGULATION:
Inhibited by Cd(2+).


RELATED PATHWAY(S):
mismatch repair (MMR)


Amino acids sequence

        10         20         30         40         50         60
MAPATPKTSK TAHFENGSTS SQKKMKQSSL LSFFSKQVPS GTPSKKVQKP TPATLENTAT
        70         80         90        100        110        120
DKITKNPQGG KTGKLFVDVD EDNDLTIAEE TVSTVRSDIM HSQEPQSDTM LNSNTTEPKS
       130        140        150        160        170        180
TTTDEDLSSS QSRRNHKRRV NYAESDDDDS DTTFTAKRKK GKVVDSESDE DEYLPDKNDG
       190        200        210        220        230        240
DEDDDIADDK EDIKGELAED SGDDDDLISL AETTSKKKFS YNTSHSSSPF TRNISRDNSK
       250        260        270        280        290        300
KKSRPNQAPS RSYNPSHSQP SATSKSSKFN KQNEERYQWL VDERDAQRRP KSDPEYDPRT
       310        320        330        340        350        360
LYIPSSAWNK FTPFEKQYWE IKSKMWDCIV FFKKGKFFEL YEKDALLANA LFDLKIAGGG
       370        380        390        400        410        420
RANMQLAGIP EMSFEYWAAQ FIQMGYKVAK VDQRESMLAK EMREGSKGIV KRELQCILTS
       430        440        450        460        470        480
GTLTDGDMLH SDLATFCLAI REEPGNFYNE TQLDSSTIVQ KLNTKIFGAA FIDTATGELQ
       490        500        510        520        530        540
MLEFEDDSEC TKLDTLMSQV RPMEVVMERN NLSTLANKIV KFNSAPNAIF NEVKAGEEFY
       550        560        570        580        590        600
DCDKTYAEII SSEYFSTEED WPEVLKSYYD TGKKVGFSAF GGLLYYLKWL KLDKNLISMK
       610        620        630        640        650        660
NIKEYDFVKS QHSMVLDGIT LQNLEIFSNS FDGSDKGTLF KLFNRAITPM GKRMMKKWLM
       670        680        690        700        710        720
HPLLRKNDIE SRLDSVDSLL QDITLREQLE ITFSKLPDLE RMLARIHSRT IKVKDFEKVI
       730        740        750        760        770        780
TAFETIIELQ DSLKNNDLKG DVSKYISSFP EGLVEAVKSW TNAFERQKAI NENIIVPQRG
       790        800        810        820        830        840
FDIEFDKSMD RIQELEDELM EILMTYRKQF KCSNIQYKDS GKEIYTIEIP ISATKNVPSN
       850        860        870        880        890        900
WVQMAANKTY KRYYSDEVRA LARSMAEAKE IHKTLEEDLK NRLCQKFDAH YNTIWMPTIQ
       910        920        930        940        950        960
AISNIDCLLA ITRTSEYLGA PSCRPTIVDE VDSKTNTQLN GFLKFKSLRH PCFNLGATTA
       970        980        990       1000       1010       1020
KDFIPNDIEL GKEQPRLGLL TGANAAGKST ILRMACIAVI MAQMGCYVPC ESAVLTPIDR
      1030       1040       1050       1060       1070       1080
IMTRLGANDN IMQGKSTFFV ELAETKKILD MATNRSLLVV DELGRGGSSS DGFAIAESVL
      1090       1100       1110       1120       1130       1140
HHVATHIQSL GFFATHYGTL ASSFKHHPQV RPLKMSILVD EATRNVTFLY KMLEGQSEGS
      1150       1160       1170       1180       1190       1200
FGMHVASMCG ISKEIIDNAQ IAADNLEHTS RLVKERDLAA NNLNGEVVSV PGGLQSDFVR
      1210       1220       1230       1240
IAYGDGLKNT KLGSGEGVLN YDWNIKRNVL KSLFSIIDDL QS 

Encoded by MSH6 gene


OTHER NAME(S):
PMS3


Nucleic acid sequence

        10         20         30         40         50         60
atggccccag ctacccctaa aacttctaag actgcacact tcgaaaatgg ctccacatct
        70         80         90        100        110        120
tctcaaaaga aaatgaagca atcgagtttg ttatcttttt tctcaaaaca ggtaccttct
       130        140        150        160        170        180
ggcacaccgt caaagaaggt ccagaagcct actccagcga ctttagaaaa tacagctact
       190        200        210        220        230        240
gataagataa caaagaatcc acaaggagga aagacaggca aacttttcgt agatgtagac
       250        260        270        280        290        300
gaagacaatg atttgacaat agctgaagaa acggtatcaa ctgtaaggag tgacataatg
       310        320        330        340        350        360
cattctcaag agccccaatc tgatactatg ttaaatagta acacgacaga acctaaaagt
       370        380        390        400        410        420
accactacgg acgaggattt atcatcttcc caatctcgaa ggaatcacaa aaggagagtg
       430        440        450        460        470        480
aattatgccg aaagtgatga tgatgactca gatactacat tcactgctaa acggaagaag
       490        500        510        520        530        540
ggtaaggtag ttgatagtga aagcgatgag gatgaatatt taccagataa aaatgacggc
       550        560        570        580        590        600
gatgaagatg acgatattgc agacgacaaa gaggacatca aaggagaatt ggcagaagat
       610        620        630        640        650        660
agtggtgatg acgatgattt aatctctctg gcagaaacga cttctaagaa aaaattttca
       670        680        690        700        710        720
tacaacactt cgcattcttc atcgcccttt acaagaaata tatcccgtga caactcaaaa
       730        740        750        760        770        780
aagaaaagca ggccaaatca ggcaccaagt agatcgtaca atccttctca tagtcaacca
       790        800        810        820        830        840
tcagcgactt ctaagtctag caaattcaat aaacaaaatg aagaacgata tcaatggtta
       850        860        870        880        890        900
gtggatgaac gagatgctca gcgccgtccc aagagtgatc cagagtacga tccaagaaca
       910        920        930        940        950        960
ctgtacatcc catcttctgc atggaacaag tttactccgt ttgaaaaaca atattgggaa
       970        980        990       1000       1010       1020
attaaatcca aaatgtggga ttgtattgtc tttttcaaaa agggtaagtt ctttgaatta
      1030       1040       1050       1060       1070       1080
tatgaaaagg atgcattatt ggctaatgca ttatttgact taaagattgc aggtggagga
      1090       1100       1110       1120       1130       1140
cgcgctaata tgcaactagc tgggattcca gagatgtcat ttgaatattg ggccgctcag
      1150       1160       1170       1180       1190       1200
tttatccaaa tgggatataa agttgcgaaa gtggatcaaa gagagtcaat gttggctaaa
      1210       1220       1230       1240       1250       1260
gaaatgaggg aaggttctaa aggtatcgtt aaaagagaac tccagtgcat attgacatcg
      1270       1280       1290       1300       1310       1320
ggtacgttaa ctgatggaga tatgttgcat tcggatctgg ctactttttg tcttgccatc
      1330       1340       1350       1360       1370       1380
agggaagaac ctggtaactt ctacaatgaa actcagctag attcatcaac gatagtgcaa
      1390       1400       1410       1420       1430       1440
aagctgaata caaaaatatt cggtgcagca ttcattgata ctgcaactgg tgagcttcaa
      1450       1460       1470       1480       1490       1500
atgctggagt ttgaagatga tagtgaatgc accaaattgg acacattaat gtcgcaagta
      1510       1520       1530       1540       1550       1560
agacctatgg aagtcgtcat ggagaggaat aacttaagca cactagctaa caaaattgta
      1570       1580       1590       1600       1610       1620
aaattcaatt cagcacccaa tgcaattttt aatgaggtta aagccggtga agaattttat
      1630       1640       1650       1660       1670       1680
gactgcgata aaacctatgc tgaaatcata tcatcagaat acttttctac ggaagaagat
      1690       1700       1710       1720       1730       1740
tggccagagg ttttgaaatc ctattatgat acgggtaaaa aagttggctt tagtgcattt
      1750       1760       1770       1780       1790       1800
ggtggattat tgtattattt gaagtggtta aaactggata agaatttaat ttcgatgaaa
      1810       1820       1830       1840       1850       1860
aatatcaaag agtacgattt tgtaaaatcg caacactcca tggttttaga tggtatcact
      1870       1880       1890       1900       1910       1920
ttacagaact tggaaatatt ttccaattcg tttgatggtt ctgataaggg tactttgttc
      1930       1940       1950       1960       1970       1980
aaattattca acagggctat tactccaatg ggtaagagaa tgatgaaaaa gtggttaatg
      1990       2000       2010       2020       2030       2040
catccattat tacgtaagaa tgatattgaa agcaggctcg atagtgttga ctctttgtta
      2050       2060       2070       2080       2090       2100
caagatatta cattaagaga acagctagag ataacatttt caaaattgcc agatttggaa
      2110       2120       2130       2140       2150       2160
agaatgttgg cccgtatcca tagtaggaca attaaagtga aagattttga aaaggtaatt
      2170       2180       2190       2200       2210       2220
accgcttttg aaacgattat tgaattacaa gactctttaa agaacaacga tttgaaggga
      2230       2240       2250       2260       2270       2280
gatgtttcaa aatacatatc ctctttccct gagggacttg tggaagctgt caaaagctgg
      2290       2300       2310       2320       2330       2340
actaatgctt ttgaaagaca aaaagcaatc aatgaaaata tcattgtacc acaaagggga
      2350       2360       2370       2380       2390       2400
tttgacatag agtttgataa gtcaatggat agaatacagg agctagaaga cgaattgatg
      2410       2420       2430       2440       2450       2460
gaaattctga tgacttatag gaagcaattc aaatgttcca atatacaata taaagattcc
      2470       2480       2490       2500       2510       2520
ggaaaggaga tatacactat tgaaattcct atctctgcaa ctaaaaatgt cccatcaaat
      2530       2540       2550       2560       2570       2580
tgggttcaaa tggctgcgaa caaaacgtac aagagatact actctgatga agtaagagct
      2590       2600       2610       2620       2630       2640
ttagcaagat cgatggcgga ggctaaagaa atacacaaga cgttagagga ggacctaaaa
      2650       2660       2670       2680       2690       2700
aatagattat gtcaaaaatt tgatgcgcat tataatacaa tttggatgcc aaccatacag
      2710       2720       2730       2740       2750       2760
gccatctcta acatagattg tttgttggca attacaagga catctgaata tctaggtgct
      2770       2780       2790       2800       2810       2820
ccctcttgta ggccaaccat tgtagatgag gtggactcga aaacgaatac tcaattaaat
      2830       2840       2850       2860       2870       2880
ggttttctga aatttaaatc attaagacat ccatgcttta acctcggcgc tactacagca
      2890       2900       2910       2920       2930       2940
aaggacttca ttcctaacga cattgaatta ggtaaagaac agcccagatt aggattgtta
      2950       2960       2970       2980       2990       3000
acgggtgcca acgcagctgg taaatccacg atattgagga tggcatgtat tgccgtaatt
      3010       3020       3030       3040       3050       3060
atggcacaaa tgggatgtta tgttccttgt gaatctgccg ttctgacgcc gattgataga
      3070       3080       3090       3100       3110       3120
atcatgactc gtttaggcgc taatgataat atcatgcaag gtaaatctac tttttttgtg
      3130       3140       3150       3160       3170       3180
gaattggcgg aaacaaaaaa aatattagac atggctacca ataggtcatt attagttgtt
      3190       3200       3210       3220       3230       3240
gacgagttgg gaagaggagg ttcatcgagt gatggttttg caattgcaga aagtgtgcta
      3250       3260       3270       3280       3290       3300
catcatgtcg cgacacatat tcaaagtctg ggtttttttg ccacacatta tgggacattg
      3310       3320       3330       3340       3350       3360
gcatcaagtt tcaagcacca tcctcaagta agaccactga aaatgagcat tctagtcgat
      3370       3380       3390       3400       3410       3420
gaagcgacta ggaacgttac atttttgtat aagatgcttg aaggacaaag tgaaggctct
      3430       3440       3450       3460       3470       3480
tttggtatgc atgttgcgtc aatgtgtggc atttcaaagg aaattattga taacgcgcag
      3490       3500       3510       3520       3530       3540
attgccgctg ataatttaga acatacttct aggctagtca aagaacgtga tttagctgca
      3550       3560       3570       3580       3590       3600
aataatttga atggtgaagt tgtctctgtg ccaggtggct tacaaagtga tttcgttcga
      3610       3620       3630       3640       3650       3660
attgcgtacg gagatggact gaagaataca aaattaggtt ctggtgaagg ggtcttgaac
      3670       3680       3690       3700       3710       3720
tatgattgga acataaaaag gaacgttttg aaaagtctat ttagtataat tgatgattta

caatcctaa     

Last modification date: Oct. 2, 2011