Homo sapiens L. (human) [HSA]

FULL NAME: DNA mismatch repair protein Msh2


DESCRIPTION:
Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta 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. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.

STRUCTURE SIMILARITY:
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.


RELATED PATHWAY(S):
mismatch repair (MMR)


RELATED DISEASE(S):
hereditary non-polyposis colorectal cancer, TYPE 8 (HNPCC8)
COLORECTAL CANCER
endometrial cancer
hereditary nonpolyposis colorectal cancer, TYPE 1 (HNPCC1), Lynch syndrome I
mismatch repair cancer syndrome (MMRCS)
Muir-Torre syndrome


Amino acids sequence

        10         20         30         40         50         60
MAVQPKETLQ LESAAEVGFV RFFQGMPEKP TTTVRLFDRG DFYTAHGEDA LLAAREVFKT
        70         80         90        100        110        120
QGVIKYMGPA GAKNLQSVVL SKMNFESFVK DLLLVRQYRV EVYKNRAGNK ASKENDWYLA
       130        140        150        160        170        180
YKASPGNLSQ FEDILFGNND MSASIGVVGV KMSAVDGQRQ VGVGYVDSIQ RKLGLCEFPD
       190        200        210        220        230        240
NDQFSNLEAL LIQIGPKECV LPGGETAGDM GKLRQIIQRG GILITERKKA DFSTKDIYQD
       250        260        270        280        290        300
LNRLLKGKKG EQMNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LTTFDFSQYM
       310        320        330        340        350        360
KLDIAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTPQGQR LVNQWIKQPL MDKNRIEERL
       370        380        390        400        410        420
NLVEAFVEDA ELRQTLQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG INQLPNVIQA
       430        440        450        460        470        480
LEKHEGKHQK LLLAVFVTPL TDLRSDFSKF QEMIETTLDM DQVENHEFLV KPSFDPNLSE
       490        500        510        520        530        540
LREIMNDLEK KMQSTLISAA RDLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS
       550        560        570        580        590        600
TVDIQKNGVK FTNSKLTSLN EEYTKNKTEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA
       610        620        630        640        650        660
QLDAVVSFAH VSNGAPVPYV RPAILEKGQG RIILKASRHA CVEVQDEIAF IPNDVYFEKD
       670        680        690        700        710        720
KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK
       730        740        750        760        770        780
GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISEYI ATKIGAFCMF
       790        800        810        820        830        840
ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPKHV
       850        860        870        880        890        900
IECAKQKALE LEEFQYIGES QGYDIMEPAA KKCYLEREQG EKIIQEFLSK VKQMPFTEMS
       910        920        930
EENITIKLKQ LKAEVIAKNN SFVNEIISRI KVTT  

Encoded by MSH2 gene

FULL NAME: mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)


OTHER NAME(S):
COCA1
FCC1
HNPCC
HNPCC1
LCFS2


DESCRIPTION:
MSH2 was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atggcggtgc agccgaagga gacgctgcag ttggagagcg cggccgaggt cggcttcgtg
        70         80         90        100        110        120
cgcttctttc agggcatgcc ggagaagccg accaccacag tgcgcctttt cgaccggggc
       130        140        150        160        170        180
gacttctata cggcgcacgg cgaggacgcg ctgctggccg cccgggaggt gttcaagacc
       190        200        210        220        230        240
cagggggtga tcaagtacat ggggccggca ggagcaaaga atctgcagag tgttgtgctt
       250        260        270        280        290        300
agtaaaatga attttgaatc ttttgtaaaa gatcttcttc tggttcgtca gtatagagtt
       310        320        330        340        350        360
gaagtttata agaatagagc tggaaataag gcatccaagg agaatgattg gtatttggca
       370        380        390        400        410        420
tataaggctt ctcctggcaa tctctctcag tttgaagaca ttctctttgg taacaatgat
       430        440        450        460        470        480
atgtcagctt ccattggtgt tgtgggtgtt aaaatgtccg cagttgatgg ccagagacag
       490        500        510        520        530        540
gttggagttg ggtatgtgga ttccatacag aggaaactag gactgtgtga attccctgat
       550        560        570        580        590        600
aatgatcagt tctccaatct tgaggctctc ctcatccaga ttggaccaaa ggaatgtgtt
       610        620        630        640        650        660
ttacccggag gagagactgc tggagacatg gggaaactga gacagataat tcaaagagga
       670        680        690        700        710        720
ggaattctga tcacagaaag aaaaaaagct gacttttcca caaaagacat ttatcaggac
       730        740        750        760        770        780
ctcaaccggt tgttgaaagg caaaaaggga gagcagatga atagtgctgt attgccagaa
       790        800        810        820        830        840
atggagaatc aggttgcagt ttcatcactg tctgcggtaa tcaagttttt agaactctta
       850        860        870        880        890        900
tcagatgatt ccaactttgg acagtttgaa ctgactactt ttgacttcag ccagtatatg
       910        920        930        940        950        960
aaattggata ttgcagcagt cagagccctt aacctttttc agggttctgt tgaagatacc
       970        980        990       1000       1010       1020
actggctctc agtctctggc tgccttgctg aataagtgta aaacccctca aggacaaaga
      1030       1040       1050       1060       1070       1080
cttgttaacc agtggattaa gcagcctctc atggataaga acagaataga ggagagattg
      1090       1100       1110       1120       1130       1140
aatttagtgg aagcttttgt agaagatgca gaattgaggc agactttaca agaagattta
      1150       1160       1170       1180       1190       1200
cttcgtcgat tcccagatct taaccgactt gccaagaagt ttcaaagaca agcagcaaac
      1210       1220       1230       1240       1250       1260
ttacaagatt gttaccgact ctatcagggt ataaatcaac tacctaatgt tatacaggct
      1270       1280       1290       1300       1310       1320
ctggaaaaac atgaaggaaa acaccagaaa ttattgttgg cagtttttgt gactcctctt
      1330       1340       1350       1360       1370       1380
actgatcttc gttctgactt ctccaagttt caggaaatga tagaaacaac tttagatatg
      1390       1400       1410       1420       1430       1440
gatcaggtgg aaaaccatga attccttgta aaaccttcat ttgatcctaa tctcagtgaa
      1450       1460       1470       1480       1490       1500
ttaagagaaa taatgaatga cttggaaaag aagatgcagt caacattaat aagtgcagcc
      1510       1520       1530       1540       1550       1560
agagatcttg gcttggaccc tggcaaacag attaaactgg attccagtgc acagtttgga
      1570       1580       1590       1600       1610       1620
tattactttc gtgtaacctg taaggaagaa aaagtccttc gtaacaataa aaactttagt
      1630       1640       1650       1660       1670       1680
actgtagata tccagaagaa tggtgttaaa tttaccaaca gcaaattgac ttctttaaat
      1690       1700       1710       1720       1730       1740
gaagagtata ccaaaaataa aacagaatat gaagaagccc aggatgccat tgttaaagaa
      1750       1760       1770       1780       1790       1800
attgtcaata tttcttcagg ctatgtagaa ccaatgcaga cactcaatga tgtgttagct
      1810       1820       1830       1840       1850       1860
cagctagatg ctgttgtcag ctttgctcac gtgtcaaatg gagcacctgt tccatatgta
      1870       1880       1890       1900       1910       1920
cgaccagcca ttttggagaa aggacaagga agaattatat taaaagcatc caggcatgct
      1930       1940       1950       1960       1970       1980
tgtgttgaag ttcaagatga aattgcattt attcctaatg acgtatactt tgaaaaagat
      1990       2000       2010       2020       2030       2040
aaacagatgt tccacatcat tactggcccc aatatgggag gtaaatcaac atatattcga
      2050       2060       2070       2080       2090       2100
caaactgggg tgatagtact catggcccaa attgggtgtt ttgtgccatg tgagtcagca
      2110       2120       2130       2140       2150       2160
gaagtgtcca ttgtggactg catcttagcc cgagtagggg ctggtgacag tcaattgaaa
      2170       2180       2190       2200       2210       2220
ggagtctcca cgttcatggc tgaaatgttg gaaactgctt ctatcctcag gtctgcaacc
      2230       2240       2250       2260       2270       2280
aaagattcat taataatcat agatgaattg ggaagaggaa cttctaccta cgatggattt
      2290       2300       2310       2320       2330       2340
gggttagcat gggctatatc agaatacatt gcaacaaaga ttggtgcttt ttgcatgttt
      2350       2360       2370       2380       2390       2400
gcaacccatt ttcatgaact tactgccttg gccaatcaga taccaactgt taataatcta
      2410       2420       2430       2440       2450       2460
catgtcacag cactcaccac tgaagagacc ttaactatgc tttatcaggt gaagaaaggt
      2470       2480       2490       2500       2510       2520
gtctgtgatc aaagttttgg gattcatgtt gcagagcttg ctaatttccc taagcatgta
      2530       2540       2550       2560       2570       2580
atagagtgtg ctaaacagaa agccctggaa cttgaggagt ttcagtatat tggagaatcg
      2590       2600       2610       2620       2630       2640
caaggatatg atatcatgga accagcagca aagaagtgct atctggaaag agagcaaggt
      2650       2660       2670       2680       2690       2700
gaaaaaatta ttcaggagtt cctgtccaag gtgaaacaaa tgccctttac tgaaatgtca
      2710       2720       2730       2740       2750       2760
gaagaaaaca tcacaataaa gttaaaacag ctaaaagctg aagtaatagc aaagaataat
      2770       2780       2790       2800
agctttgtaa atgaaatcat ttcacgaata aaagttacta cgtga 

Last modification date: Oct. 2, 2011