Homo sapiens L. (human) [HSA]

FULL NAME: Werner syndrome ATP-dependent helicase


DESCRIPTION:
Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity).
The gene (WRN) defective in WS encodes a 1432-amino acid protein (WRN) that has ATPase, 3′ → 5′-helicase and 3′ → 5′-exonuclease activities. WRN (WRNp) is a member of the RecQ family of DNA helicases, which also includes yeast Saccharomyces cerevisiae Sgs1, and four other human members, including the genes mutated in Bloom's Syndrome (BLM)  and in Rothmund-Thomson's Syndrome (RecQL4). Bloom's Syndrome and Rothmund-Thomson's Syndrome resemble WS, in that they are characterized by a predisposition to malignancies and increased genomic instability. Therefore, the RecQ helicases appear to play important biological roles, most probably relating to DNA metabolism.

STRUCTURE SIMILARITY:
Contains 1 helicase ATP-binding domain.
Contains 1 HRDC domain.
Contains 1 helicase C-terminal domain.
Contains 1 3'-5' exonuclease domain.
Belongs to the helicase family. RecQ subfamily.


CATALYTIC ACTIVITY:
ATP + H(2)O = ADP + phosphate.


POST-TRANSLATIONAL MODIFICATION:
Phosphorylated by PRKDC. Phosphorylated upon DNA damage, probably by ATM or ATR.


PROTEIN TYPE(S):
3'-5' exonuclease
3'-5' DNA helicase
DNase


RELATED DISEASE(S):
Werner syndrome (WRN)


Amino acids sequence

        10         20         30         40         50         60
MSEKKLETTA QQRKCPEWMN VQNKRCAVEE RKACVRKSVF EDDLPFLEFT GSIVYSYDAS
        70         80         90        100        110        120
DCSFLSEDIS MSLSDGDVVG FDMEWPPLYN RGKLGKVALI QLCVSESKCY LFHVSSMSVF
       130        140        150        160        170        180
PQGLKMLLEN KAVKKAGVGI EGDQWKLLRD FDIKLKNFVE LTDVANKKLK CTETWSLNSL
       190        200        210        220        230        240
VKHLLGKQLL KDKSIRCSNW SKFPLTEDQK LYAATDAYAG FIIYRNLEIL DDTVQRFAIN
       250        260        270        280        290        300
KEEEILLSDM NKQLTSISEE VMDLAKHLPH AFSKLENPRR VSILLKDISE NLYSLRRMII
       310        320        330        340        350        360
GSTNIETELR PSNNLNLLSF EDSTTGGVQQ KQIREHEVLI HVEDETWDPT LDHLAKHDGE
       370        380        390        400        410        420
DVLGNKVERK EDGFEDGVED NKLKENMERA CLMSLDITEH ELQILEQQSQ EEYLSDIAYK
       430        440        450        460        470        480
STEHLSPNDN ENDTSYVIES DEDLEMEMLK HLSPNDNEND TSYVIESDED LEMEMLKSLE
       490        500        510        520        530        540
NLNSGTVEPT HSKCLKMERN LGLPTKEEEE DDENEANEGE EDDDKDFLWP APNEEQVTCL
       550        560        570        580        590        600
KMYFGHSSFK PVQWKVIHSV LEERRDNVAV MATGYGKSLC FQYPPVYVGK IGLVISPLIS
       610        620        630        640        650        660
LMEDQVLQLK MSNIPACFLG SAQSENVLTD IKLGKYRIVY VTPEYCSGNM GLLQQLEADI
       670        680        690        700        710        720
GITLIAVDEA HCISEWGHDF RDSFRKLGSL KTALPMVPIV ALTATASSSI REDIVRCLNL
       730        740        750        760        770        780
RNPQITCTGF DRPNLYLEVR RKTGNILQDL QPFLVKTSSH WEFEGPTIIY CPSRKMTQQV
       790        800        810        820        830        840
TGELRKLNLS CGTYHAGMSF STRKDIHHRF VRDEIQCVIA TIAFGMGINK ADIRQVIHYG
       850        860        870        880        890        900
APKDMESYYQ EIGRAGRDGL QSSCHVLWAP ADINLNRHLL TEIRNEKFRL YKLKMMAKME
       910        920        930        940        950        960
KYLHSSRCRR QIILSHFEDK QVQKASLGIM GTEKCCDNCR SRLDHCYSMD DSEDTSWDFG
       970        980        990       1000       1010       1020
PQAFKLLSAV DILGEKFGIG LPILFLRGSN SQRLADQYRR HSLFGTGKDQ TESWWKAFSR
      1030       1040       1050       1060       1070       1080
QLITEGFLVE VSRYNKFMKI CALTKKGRNW LHKANTESQS LILQANEELC PKKLLLPSSK
      1090       1100       1110       1120       1130       1140
TVSSGTKEHC YNQVPVELST EKKSNLEKLY SYKPCDKISS GSNISKKSIM VQSPEKAYSS
      1150       1160       1170       1180       1190       1200
SQPVISAQEQ ETQIVLYGKL VEARQKHANK MDVPPAILAT NKILVDMAKM RPTTVENVKR
      1210       1220       1230       1240       1250       1260
IDGVSEGKAA MLAPLLEVIK HFCQTNSVQT DLFSSTKPQE EQKTSLVAKN KICTLSQSMA
      1270       1280       1290       1300       1310       1320
ITYSLFQEKK MPLKSIAESR ILPLMTIGMH LSQAVKAGCP LDLERAGLTP EVQKIIADVI
      1330       1340       1350       1360       1370       1380
RNPPVNSDMS KISLIRMLVP ENIDTYLIHM AIEILKHGPD SGLQPSCDVN KRRCFPGSEE
      1390       1400       1410       1420       1430
ICSSSKRSKE EVGINTETSS AERKRRLPVW FAKGSDTSKK LMDKTKRGGL FS

Encoded by WRN gene

FULL NAME: Werner syndrome, RecQ helicase-like


OTHER NAME(S):
DKFZp686C2056
RECQ3
RECQL2
RECQL3


DESCRIPTION:
This gene encodes a member of the RecQ subfamily and the DEAH (Asp-Glu-Ala-His) subfamily of DNA and RNA helicases. DNA helicases are involved in many aspects of DNA metabolism, including transcription, replication, recombination, and repair. This protein contains a nuclear localization signal in the C-terminus and shows a predominant nucleolar localization. It possesses an intrinsic 3' to 5' DNA helicase activity, and is also a 3' to 5' exonuclease. Based on interactions between this protein and Ku70/80 heterodimer in DNA end processing, this protein may be involved in the repair of double strand DNA breaks. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by premature aging. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atgagtgaaa aaaaattgga aacaactgca cagcagcgga aatgtcctga atggatgaat
        70         80         90        100        110        120
gtgcagaata aaagatgtgc tgtagaagaa agaaaggcat gtgttcggaa gagtgttttt
       130        140        150        160        170        180
gaagatgacc tccccttctt agaattcact ggatccattg tgtatagtta cgatgctagt
       190        200        210        220        230        240
gattgctctt tcctgtcaga agatattagc atgagtctat cagatgggga tgtggtggga
       250        260        270        280        290        300
tttgacatgg agtggccacc attatacaat agagggaaac ttggcaaagt tgcactaatt
       310        320        330        340        350        360
cagttgtgtg tttctgagag caaatgttac ttgttccacg tttcttccat gtcagttttt
       370        380        390        400        410        420
ccccagggat taaaaatgtt gcttgaaaat aaagcagtta aaaaggcagg tgtaggaatt
       430        440        450        460        470        480
gaaggagatc agtggaaact tctacgtgac tttgatatca aattgaagaa ttttgtggag
       490        500        510        520        530        540
ttgacagatg ttgccaataa aaagctgaaa tgcacagaga cctggagcct taacagtctg
       550        560        570        580        590        600
gttaaacacc tcttaggtaa acagctcctg aaagacaagt ctatccgctg tagcaattgg
       610        620        630        640        650        660
agtaaatttc ctctcactga ggaccagaaa ctgtatgcag ccactgatgc ttatgctggt
       670        680        690        700        710        720
tttattattt accgaaattt agagattttg gatgatactg tgcaaaggtt tgctataaat
       730        740        750        760        770        780
aaagaggaag aaatcctact tagcgacatg aacaaacagt tgacttcaat ctctgaggaa
       790        800        810        820        830        840
gtgatggatc tggctaagca tcttcctcat gctttcagta aattggaaaa cccacggagg
       850        860        870        880        890        900
gtttctatct tactaaagga tatttcagaa aatctatatt cactgaggag gatgataatt
       910        920        930        940        950        960
gggtctacta acattgagac tgaactgagg cccagcaata atttaaactt attatccttt
       970        980        990       1000       1010       1020
gaagattcaa ctactggggg agtacaacag aaacaaatta gagaacatga agttttaatt
      1030       1040       1050       1060       1070       1080
cacgttgaag atgaaacatg ggacccaaca cttgatcatt tagctaaaca tgatggagaa
      1090       1100       1110       1120       1130       1140
gatgtacttg gaaataaagt ggaacgaaaa gaagatggat ttgaagatgg agtagaagac
      1150       1160       1170       1180       1190       1200
aacaaattga aagagaatat ggaaagagct tgtttgatgt cgttagatat tacagaacat
      1210       1220       1230       1240       1250       1260
gaactccaaa ttttggaaca gcagtctcag gaagaatatc ttagtgatat tgcttataaa
      1270       1280       1290       1300       1310       1320
tctactgagc atttatctcc caatgataat gaaaacgata cgtcctatgt aattgagagt
      1330       1340       1350       1360       1370       1380
gatgaagatt tagaaatgga gatgcttaag catttatctc ccaatgataa tgaaaacgat
      1390       1400       1410       1420       1430       1440
acgtcctatg taattgagag tgatgaagat ttagaaatgg agatgcttaa gtctttagaa
      1450       1460       1470       1480       1490       1500
aacctcaata gtggcacggt agaaccaact cattctaaat gcttaaaaat ggaaagaaat
      1510       1520       1530       1540       1550       1560
ctgggtcttc ctactaaaga agaagaagaa gatgatgaaa atgaagctaa tgaaggggaa
      1570       1580       1590       1600       1610       1620
gaagatgatg ataaggactt tttgtggcca gcacccaatg aagagcaagt tacttgcctc
      1630       1640       1650       1660       1670       1680
aagatgtact ttggccattc cagttttaaa ccagttcagt ggaaagtgat tcattcagta
      1690       1700       1710       1720       1730       1740
ttagaagaaa gaagagataa tgttgctgtc atggcaactg gatatggaaa gagtttgtgc
      1750       1760       1770       1780       1790       1800
ttccagtatc cacctgttta tgtaggcaag attggccttg ttatctctcc ccttatttct
      1810       1820       1830       1840       1850       1860
ctgatggaag accaagtgct acagcttaaa atgtccaaca tcccagcttg cttccttgga
      1870       1880       1890       1900       1910       1920
tcagcacagt cagaaaatgt tctaacagat attaaattag gtaaataccg gattgtatac
      1930       1940       1950       1960       1970       1980
gtaactccag aatactgttc aggtaacatg ggcctgctcc agcaacttga ggctgatatt
      1990       2000       2010       2020       2030       2040
ggtatcacgc tcattgctgt ggatgaggct cactgtattt ctgagtgggg gcatgatttt
      2050       2060       2070       2080       2090       2100
agggattcat tcaggaagtt gggctcccta aagacagcac tgccaatggt tccaatcgtt
      2110       2120       2130       2140       2150       2160
gcacttactg ctactgcaag ttcttcaatc cgggaagaca ttgtacgttg cttaaatctg
      2170       2180       2190       2200       2210       2220
agaaatcctc agatcacctg tactggtttt gatcgaccaa acctgtattt agaagttagg
      2230       2240       2250       2260       2270       2280
cgaaaaacag ggaatatcct tcaggatctg cagccatttc ttgtcaaaac aagttcccac
      2290       2300       2310       2320       2330       2340
tgggaatttg aaggtccaac aatcatctac tgtccttcta gaaaaatgac acaacaagtt
      2350       2360       2370       2380       2390       2400
acaggtgaac ttaggaaact gaatctatcc tgtggaacat accatgcggg catgagtttt
      2410       2420       2430       2440       2450       2460
agcacaagga aagacattca tcataggttt gtaagagatg aaattcagtg tgtcatagct
      2470       2480       2490       2500       2510       2520
accatagctt ttggaatggg cattaataaa gctgacattc gccaagtcat tcattacggt
      2530       2540       2550       2560       2570       2580
gctcctaagg acatggaatc atattatcag gagattggta gagctggtcg tgatggactt
      2590       2600       2610       2620       2630       2640
caaagttctt gtcacgtcct ctgggctcct gcagacatta acttaaatag gcaccttctt
      2650       2660       2670       2680       2690       2700
actgagatac gtaatgagaa gtttcgatta tacaaattaa agatgatggc aaagatggaa
      2710       2720       2730       2740       2750       2760
aaatatcttc attctagcag atgtaggaga caaatcatct tgtctcattt tgaggacaaa
      2770       2780       2790       2800       2810       2820
caagtacaaa aagcctcctt gggaattatg ggaactgaaa aatgctgtga taattgcagg
      2830       2840       2850       2860       2870       2880
tccagattgg atcattgcta ttccatggat gactcagagg atacatcctg ggactttggt
      2890       2900       2910       2920       2930       2940
ccacaagcat ttaagctttt gtctgctgtg gacatcttag gcgaaaaatt tggaattggg
      2950       2960       2970       2980       2990       3000
cttccaattt tatttctccg aggatctaat tctcagcgtc ttgccgatca atatcgcagg
      3010       3020       3030       3040       3050       3060
cacagtttat ttggcactgg caaggatcaa acagagagtt ggtggaaggc tttttcccgt
      3070       3080       3090       3100       3110       3120
cagctgatca ctgagggatt cttggtagaa gtttctcggt ataacaaatt tatgaagatt
      3130       3140       3150       3160       3170       3180
tgcgccctta cgaaaaaggg tagaaattgg cttcataaag ctaatacaga atctcagagc
      3190       3200       3210       3220       3230       3240
ctcatccttc aagctaatga agaattgtgt ccaaagaagt tgcttctgcc tagttcgaaa
      3250       3260       3270       3280       3290       3300
actgtatctt cgggcaccaa agagcattgt tataatcaag taccagttga attaagtaca
      3310       3320       3330       3340       3350       3360
gagaagaagt ctaacttgga gaagttatat tcttataaac catgtgataa gatttcttct
      3370       3380       3390       3400       3410       3420
gggagtaaca tttctaaaaa aagtatcatg gtacagtcac cagaaaaagc ttacagttcc
      3430       3440       3450       3460       3470       3480
tcacagcctg ttatttcggc acaagagcag gagactcaga ttgtgttata tggcaaattg
      3490       3500       3510       3520       3530       3540
gtagaagcta ggcagaaaca tgccaataaa atggatgttc ccccagctat tctggcaaca
      3550       3560       3570       3580       3590       3600
aacaagatac tggtggatat ggccaaaatg agaccaacta cggttgaaaa cgtaaaaagg
      3610       3620       3630       3640       3650       3660
attgatggtg tttctgaagg caaagctgcc atgttggccc ctctgttgga agtcatcaaa
      3670       3680       3690       3700       3710       3720
catttctgcc aaacaaatag tgttcagaca gacctctttt caagtacaaa acctcaagaa
      3730       3740       3750       3760       3770       3780
gaacagaaga cgagtctggt agcaaaaaat aaaatatgca cactttcaca gtctatggcc
      3790       3800       3810       3820       3830       3840
atcacatact ctttattcca agaaaagaag atgcctttga agagcatagc tgagagcagg
      3850       3860       3870       3880       3890       3900
attctgcctc tcatgacaat tggcatgcac ttatcccaag cggtgaaagc tggctgcccc
      3910       3920       3930       3940       3950       3960
cttgatttgg agcgagcagg cctgactcca gaggttcaga agattattgc tgatgttatc
      3970       3980       3990       4000       4010       4020
cgaaaccctc ccgtcaactc agatatgagt aaaattagcc taatcagaat gttagttcct
      4030       4040       4050       4060       4070       4080
gaaaacattg acacgtacct tatccacatg gcaattgaga tccttaaaca tggtcctgac
      4090       4100       4110       4120       4130       4140
agcggacttc aaccttcatg tgatgtcaac aaaaggagat gttttcccgg ttctgaagag
      4150       4160       4170       4180       4190       4200
atctgttcaa gttctaagag aagcaaggaa gaagtaggca tcaatactga gacttcatct
      4210       4220       4230       4240       4250       4260
gcagagagaa agagacgatt acctgtgtgg tttgccaaag gaagtgatac cagcaagaaa
      4270       4280       4290
ttaatggaca aaacgaaaag gggaggtctt tttagttaa  

Last modification date: Oct. 2, 2011