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
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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.
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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.
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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:
- 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:
- 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.
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References |
- 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
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