Homo sapiens L. (human) [HSA]

FULL NAME: Mismatch repair endonuclease PMS2


DESCRIPTION:
Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MulL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages.

STRUCTURE SIMILARITY:
Belongs to the DNA mismatch repair mutL/hexB family.


RELATED PATHWAY(S):
Fanconi anemia (FA) pathway
mismatch repair (MMR)


RELATED DISEASE(S):
mismatch repair cancer syndrome (MMRCS)
COLORECTAL CANCER
hereditary non-polyposis colorectal cancer, TYPE 4


Amino acids sequence

        10         20         30         40         50         60
MERAESSSTE PAKAIKPIDR KSVHQICSGQ VVLSLSTAVK ELVENSLDAG ATNIDLKLKD
        70         80         90        100        110        120
YGVDLIEVSD NGCGVEEENF EGLTLKHHTS KIQEFADLTQ VETFGFRGEA LSSLCALSDV
       130        140        150        160        170        180
TISTCHASAK VGTRLMFDHN GKIIQKTPYP RPRGTTVSVQ QLFSTLPVRH KEFQRNIKKE
       190        200        210        220        230        240
YAKMVQVLHA YCIISAGIRV SCTNQLGQGK RQPVVCTGGS PSIKENIGSV FGQKQLQSLI
       250        260        270        280        290        300
PFVQLPPSDS VCEEYGLSCS DALHNLFYIS GFISQCTHGV GRSSTDRQFF FINRRPCDPA
       310        320        330        340        350        360
KVCRLVNEVY HMYNRHQYPF VVLNISVDSE CVDINVTPDK RQILLQEEKL LLAVLKTSLI
       370        380        390        400        410        420
GMFDSDVNKL NVSQQPLLDV EGNLIKMHAA DLEKPMVEKQ DQSPSLRTGE EKKDVSISRL
       430        440        450        460        470        480
REAFSLRHTT ENKPHSPKTP EPRRSPLGQK RGMLSSSTSG AISDKGVLRP QKEAVSSSHG
       490        500        510        520        530        540
PSDPTDRAEV EKDSGHGSTS VDSEGFSIPD TGSHCSSEYA ASSPGDRGSQ EHVDSQEKAP
       550        560        570        580        590        600
ETDDSFSDVD CHSNQEDTGC KFRVLPQPTN LATPNTKRFK KEEILSSSDI CQKLVNTQDM
       610        620        630        640        650        660
SASQVDVAVK INKKVVPLDF SMSSLAKRIK QLHHEAQQSE GEQNYRKFRA KICPGENQAA
       670        680        690        700        710        720
EDELRKEISK TMFAEMEIIG QFNLGFIITK LNEDIFIVDQ HATDEKYNFE MLQQHTVLQG
       730        740        750        760        770        780
QRLIAPQTLN LTAVNEAVLI ENLEIFRKNG FDFVIDENAP VTERAKLISL PTSKNWTFGP
       790        800        810        820        830        840
QDVDELIFML SDSPGVMCRP SRVKQMFASR ACRKSVMIGT ALNTSEMKKL ITHMGEMDHP
       850        860
WNCPHGRPTM RHIANLGVIS QN   

Encoded by PMS2 gene

FULL NAME: PMS2 postmeiotic segregation increased 2 (S. cerevisiae)


OTHER NAME(S):
HNPCC4
PMS2CL
PMSL2


DESCRIPTION:
This gene is one of the PMS2 gene family members found in clusters on chromosome 7. The product of this gene is involved in DNA mismatch repair. It forms a heterodimer with MLH1 and this complex interacts with other complexes bound to mismatched bases. Mutations in this gene are associated with hereditary nonpolyposis colorectal cancer, Turcot syndrome, and are a cause of supratentorial primitive neuroectodermal tumors. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atggagcgag ctgagagctc gagtacagaa cctgctaagg ccatcaaacc tattgatcgg
        70         80         90        100        110        120
aagtcagtcc atcagatttg ctctgggcag gtggtactga gtctaagcac tgcggtaaag
       130        140        150        160        170        180
gagttagtag aaaacagtct ggatgctggt gccactaata ttgatctaaa gcttaaggac
       190        200        210        220        230        240
tatggagtgg atcttattga agtttcagac aatggatgtg gggtagaaga agaaaacttc
       250        260        270        280        290        300
gaaggcttaa ctctgaaaca tcacacatct aagattcaag agtttgccga cctaactcag
       310        320        330        340        350        360
gttgaaactt ttggctttcg gggggaagct ctgagctcac tttgtgcact gagcgatgtc
       370        380        390        400        410        420
accatttcta cctgccacgc atcggcgaag gttggaactc gactgatgtt tgatcacaat
       430        440        450        460        470        480
gggaaaatta tccagaaaac cccctacccc cgccccagag ggaccacagt cagcgtgcag
       490        500        510        520        530        540
cagttatttt ccacactacc tgtgcgccat aaggaatttc aaaggaatat taagaaggag
       550        560        570        580        590        600
tatgccaaaa tggtccaggt cttacatgca tactgtatca tttcagcagg catccgtgta
       610        620        630        640        650        660
agttgcacca atcagcttgg acaaggaaaa cgacagcctg tggtatgcac aggtggaagc
       670        680        690        700        710        720
cccagcataa aggaaaatat cggctctgtg tttgggcaga agcagttgca aagcctcatt
       730        740        750        760        770        780
ccttttgttc agctgccccc tagtgactcc gtgtgtgaag agtacggttt gagctgttcc
       790        800        810        820        830        840
gatgctctgc ataatctttt ttacatctca ggtttcattt cacaatgcac gcatggagtt
       850        860        870        880        890        900
ggaaggagtt caacagacag acagtttttc tttatcaacc ggcggccttg tgacccagca
       910        920        930        940        950        960
aaggtctgca gactcgtgaa tgaggtctac cacatgtata atcgacacca gtatccattt
       970        980        990       1000       1010       1020
gttgttctta acatttctgt tgattcagaa tgcgttgata tcaatgttac tccagataaa
      1030       1040       1050       1060       1070       1080
aggcaaattt tgctacaaga ggaaaagctt ttgttggcag ttttaaagac ctctttgata
      1090       1100       1110       1120       1130       1140
ggaatgtttg atagtgatgt caacaagcta aatgtcagtc agcagccact gctggatgtt
      1150       1160       1170       1180       1190       1200
gaaggtaact taataaaaat gcatgcagcg gatttggaaa agcccatggt agaaaagcag
      1210       1220       1230       1240       1250       1260
gatcaatccc cttcattaag gactggagaa gaaaaaaaag acgtgtccat ttccagactg
      1270       1280       1290       1300       1310       1320
cgagaggcct tttctcttcg tcacacaaca gagaacaagc ctcacagccc aaagactcca
      1330       1340       1350       1360       1370       1380
gaaccaagaa ggagccctct aggacagaaa aggggtatgc tgtcttctag cacttcaggt
      1390       1400       1410       1420       1430       1440
gccatctctg acaaaggcgt cctgagacct cagaaagagg cagtgagttc cagtcacgga
      1450       1460       1470       1480       1490       1500
cccagtgacc ctacggacag agcggaggtg gagaaggact cggggcacgg cagcacttcc
      1510       1520       1530       1540       1550       1560
gtggattctg aggggttcag catcccagac acgggcagtc actgcagcag cgagtatgcg
      1570       1580       1590       1600       1610       1620
gccagctccc caggggacag gggctcgcag gaacatgtgg actctcagga gaaagcgcct
      1630       1640       1650       1660       1670       1680
gaaactgacg actctttttc agatgtggac tgccattcaa accaggaaga taccggatgt
      1690       1700       1710       1720       1730       1740
aaatttcgag ttttgcctca gccaactaat ctcgcaaccc caaacacaaa gcgttttaaa
      1750       1760       1770       1780       1790       1800
aaagaagaaa ttctttccag ttctgacatt tgtcaaaagt tagtaaatac tcaggacatg
      1810       1820       1830       1840       1850       1860
tcagcctctc aggttgatgt agctgtgaaa attaataaga aagttgtgcc cctggacttt
      1870       1880       1890       1900       1910       1920
tctatgagtt ctttagctaa acgaataaag cagttacatc atgaagcaca gcaaagtgaa
      1930       1940       1950       1960       1970       1980
ggggaacaga attacaggaa gtttagggca aagatttgtc ctggagaaaa tcaagcagcc
      1990       2000       2010       2020       2030       2040
gaagatgaac taagaaaaga gataagtaaa acgatgtttg cagaaatgga aatcattggt
      2050       2060       2070       2080       2090       2100
cagtttaacc tgggatttat aataaccaaa ctgaatgagg atatcttcat agtggaccag
      2110       2120       2130       2140       2150       2160
catgccacgg acgagaagta taacttcgag atgctgcagc agcacaccgt gctccagggg
      2170       2180       2190       2200       2210       2220
cagaggctca tagcacctca gactctcaac ttaactgctg ttaatgaagc tgttctgata
      2230       2240       2250       2260       2270       2280
gaaaatctgg aaatatttag aaagaatggc tttgattttg ttatcgatga aaatgctcca
      2290       2300       2310       2320       2330       2340
gtcactgaaa gggctaaact gatttccttg ccaactagta aaaactggac cttcggaccc
      2350       2360       2370       2380       2390       2400
caggacgtcg atgaactgat cttcatgctg agcgacagcc ctggggtcat gtgccggcct
      2410       2420       2430       2440       2450       2460
tcccgagtca agcagatgtt tgcctccaga gcctgccgga agtcggtgat gattgggact
      2470       2480       2490       2500       2510       2520
gctcttaaca caagcgagat gaagaaactg atcacccaca tgggggagat ggaccacccc
      2530       2540       2550       2560       2570       2580
tggaactgtc cccatggaag gccaaccatg agacacatcg ccaacctggg tgtcatttct

cagaactga     

Last modification date: Oct. 2, 2011