DP00443: Werner syndrome ATP-dependent helicaseFASTA viewXML view

General information
DisProt:DP00443
Name:Werner syndrome ATP-dependent helicase
Synonym(s):WRN_HUMAN
First appeared in release:Release 3.0 (02/17/2006)
UniProt:Q14191
UniGene:Hs.632050
SwissProt: WRN_HUMAN
TrEMBL:  
NCBI (GI): 6136393
Source organism:Homo sapiens (Human)
Sequence length:1432
Percent disordered:2%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MSEKKLETTA QQRKCPEWMN VQNKRCAVEE RKACVRKSVF EDDLPFLEFT GSIVYSYDAS - 60
DCSFLSEDIS MSLSDGDVVG FDMEWPPLYN RGKLGKVALI QLCVSESKCY LFHVSSMSVF - 120
PQGLKMLLEN KAVKKAGVGI EGDQWKLLRD FDIKLKNFVE LTDVANKKLK CTETWSLNSL - 180
VKHLLGKQLL KDKSIRCSNW SKFPLTEDQK LYAATDAYAG FIIYRNLEIL DDTVQRFAIN - 240
KEEEILLSDM NKQLTSISEE VMDLAKHLPH AFSKLENPRR VSILLKDISE NLYSLRRMII - 300
GSTNIETELR PSNNLNLLSF EDSTTGGVQQ KQIREHEVLI HVEDETWDPT LDHLAKHDGE - 360
DVLGNKVERK EDGFEDGVED NKLKENMERA CLMSLDITEH ELQILEQQSQ EEYLSDIAYK - 420
STEHLSPNDN ENDTSYVIES DEDLEMEMLK HLSPNDNEND TSYVIESDED LEMEMLKSLE - 480
NLNSGTVEPT HSKCLKMERN LGLPTKEEEE DDENEANEGE EDDDKDFLWP APNEEQVTCL - 540
KMYFGHSSFK PVQWKVIHSV LEERRDNVAV MATGYGKSLC FQYPPVYVGK IGLVISPLIS - 600
LMEDQVLQLK MSNIPACFLG SAQSENVLTD IKLGKYRIVY VTPEYCSGNM GLLQQLEADI - 660
GITLIAVDEA HCISEWGHDF RDSFRKLGSL KTALPMVPIV ALTATASSSI REDIVRCLNL - 720
RNPQITCTGF DRPNLYLEVR RKTGNILQDL QPFLVKTSSH WEFEGPTIIY CPSRKMTQQV - 780
TGELRKLNLS CGTYHAGMSF STRKDIHHRF VRDEIQCVIA TIAFGMGINK ADIRQVIHYG - 840
APKDMESYYQ EIGRAGRDGL QSSCHVLWAP ADINLNRHLL TEIRNEKFRL YKLKMMAKME - 900
KYLHSSRCRR QIILSHFEDK QVQKASLGIM GTEKCCDNCR SRLDHCYSMD DSEDTSWDFG - 960
PQAFKLLSAV DILGEKFGIG LPILFLRGSN SQRLADQYRR HSLFGTGKDQ TESWWKAFSR - 1020
QLITEGFLVE VSRYNKFMKI CALTKKGRNW LHKANTESQS LILQANEELC PKKFLLPSSK - 1080
TVSSGTKEHC YNQVPVELST EKKSNLEKLY SYKPCDKISS GSNISKKSIM VQSPEKAYSS - 1140
SQPVISAQEQ ETQIVLYGKL VEARQKHANK MDVPPAILAT NKILVDMAKM RPTTVENVKR - 1200
IDGVSEGKAA MLAPLLEVIK HFCQTNSVQT DLFSSTKPQE EQKTSLVAKN KICTLSQSMA - 1260
ITYSLFQEKK MPLKSIAESR ILPLMTIGMH LSQAVKAGCP LDLERAGLTP EVQKIIADVI - 1320
RNPPVNSDMS KISLIRMLVP ENIDTYLIHM AIEILKHGPD SGLQPSCDVN KRRCFPGSEE - 1380
ICSSSKRSKE EVGINTETSS AERKRRLPVW FAKGSDTSKK LMDKTKRGGL FS



Functional narrative    

Werner syndrome (WS) is an autosomal recessive disease that results in premature aging. WS patients age rapidly after puberty, with the accelerated development of atherosclerosis, arteriosclerosis, graying and loss of hair, type II diabetes, bilateral cataracts, osteoporosis, and thymic atrophy. These individuals are predisposed to the emergence of benign and malignant neoplasm. Mutations in the WS gene (WRN) result in a loss of expression of the WRN protein and predispose WS patients to accelerated aging. As a helicase and a nuclease, WRN is unique among the five human RecQ helicase family members and is capable of multiple functions involved in DNA replication, repair, recombination, and telomere maintenance. WRN also contains four other domains: a nuclease, a RecQ carboxy (RQC), a helicase-and-ribonuclease D-C-terminal (HRDC), and a nuclear localization signal (NLS) domain. A 144-residue fragment of WRN was previously determined to be a multifunctional DNA- and protein-binding domain (DPBD) that interacts with structure-specific DNA and a variety of DNA-processing proteins. In addition, DPBD functions as a nucleolar targeting sequence of WRN. Most mutations identified in WS patients result in C-terminal truncated WRN proteins missing NLS. The inability of WRN to be transported into the nucleus seems to be crucial for the pathogenesis of WS. Inside the nucleus, WRN is located mainly in the nucleoli and in nuclear foci. The specific regions of WRN that are responsible for this localization have been mapped to this 144-residue fragment (amino acids 949-1092) and a NLS-containing C-terminal fragment. Essential for the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity. May be involved in the control of genomic stability.

Region 1: 1069-1092

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 1
Type:Disordered
Name: 
Location:1069 - 1092
Length:24
Region sequence:

LCPKKFLLPSSKTVSSGTKEHCYN

Modification type: Fragment
Native
PDB: 2AXL:A
Structural/functional type: Relationship to function unknown
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (295 K; pH: 7.4; 0.35 mM labeled protein (Uniform 15N and 13C labeling); 25 mM KPi, 25 mM NaCl, 4 mM d10-DTT, 1 mM d16-EDTA; 92.5% H2O, 7.5% D2O)

References:
  1. Hu JS, Feng H, Zeng W, Lin GX, Xi XG. "Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein." Proc Natl Acad Sci U S A. 2005; 102(51): 18379–18384. PubMed: 16339893

Comments:
The solution structure of the DPBD, the first of a WRN fragment, has been solved by NMR. DPBD consists of a winged helix-like motif and an unstructured C-terminal region of 24 aa.




References

  1. Ozgenc A, Loeb LA. "Current advances in unraveling the function of the Werner syndrome protein." Mutat Res. 2005; 577((1-2)): 237-51. PubMed: 15946710


If you have any comments or wish to provide additional references to this protein or its disordered region(s), please click here to e-mail us.


Disprot-footer
Contact us