Overview
| Uniprot ID | Q14191 |
|---|
| Protein Name | Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN |
|---|
| Gene Name | WRN |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 1126 |
SSGSNISKKSIMVQS |
| 14 |
ETTAQQRKCPEWMNV |
| 934 |
LGIMGTEKCCDNCRS |
Function
Multifunctional enzyme that has magnesium and ATP-dependent 3'-5' DNA-helicase activity on partially duplex substrates (PubMed:9224595, PubMed:9288107, PubMed:9611231). Also has 3'->5' exonuclease activity towards double-stranded (ds)DNA with a 5'-overhang (PubMed:11863428). Has no nuclease activity towards single-stranded (ss)DNA or blunt-ended dsDNA (PubMed:11863428). Helicase activity is most efficient with (d)ATP, but (d)CTP will substitute with reduced efficiency; strand displacement is enhanced by single-strand binding-protein (heterotrimeric replication protein A complex, RPA1, RPA2, RPA3) (PubMed:9611231). 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. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity). Plays a role in double-strand break repair after gamma-irradiation (PubMed:9224595, PubMed:9288107, PubMed:9611231). Unwinds some G-quadruplex DNA (d(CGG)n tracts); unwinding seems to occur in both 5'-3' and 3'-5' direction and requires a short single-stranded tail (PubMed:10212265). d(CGG)n tracts have a propensity to assemble into tetraplex structures; other G-rich substrates from a telomeric or IgG switch sequence are not unwound (PubMed:10212265). Depletion leads to chromosomal breaks and genome instability (PubMed:33199508)
Protein Sequence
10
MSEKKLETTA
20
QQRKCPEWMN
30
VQNKRCAVEE
40
RKACVRKSVF
50
EDDLPFLEFT
60
GSIVYSYDAS
70
DCSFLSEDIS
80
MSLSDGDVVG
90
FDMEWPPLYN
100
RGKLGKVALI
110
QLCVSESKCY
120
LFHVSSMSVF
130
PQGLKMLLEN
140
KAVKKAGVGI
150
EGDQWKLLRD
160
FDIKLKNFVE
170
LTDVANKKLK
180
CTETWSLNSL
190
VKHLLGKQLL
200
KDKSIRCSNW
210
SKFPLTEDQK
220
LYAATDAYAG
230
FIIYRNLEIL
240
DDTVQRFAIN
250
KEEEILLSDM
260
NKQLTSISEE
270
VMDLAKHLPH
280
AFSKLENPRR
290
VSILLKDISE
300
NLYSLRRMII
310
GSTNIETELR
320
PSNNLNLLSF
330
EDSTTGGVQQ
340
KQIREHEVLI
350
HVEDETWDPT
360
LDHLAKHDGE
370
DVLGNKVERK
380
EDGFEDGVED
390
NKLKENMERA
400
CLMSLDITEH
410
ELQILEQQSQ
420
EEYLSDIAYK
430
STEHLSPNDN
440
ENDTSYVIES
450
DEDLEMEMLK
460
HLSPNDNEND
470
TSYVIESDED
480
LEMEMLKSLE
490
NLNSGTVEPT
500
HSKCLKMERN
510
LGLPTKEEEE
520
DDENEANEGE
530
EDDDKDFLWP
540
APNEEQVTCL
550
KMYFGHSSFK
560
PVQWKVIHSV
570
LEERRDNVAV
580
MATGYGKSLC
590
FQYPPVYVGK
600
IGLVISPLIS
610
LMEDQVLQLK
620
MSNIPACFLG
630
SAQSENVLTD
640
IKLGKYRIVY
650
VTPEYCSGNM
660
GLLQQLEADI
670
GITLIAVDEA
680
HCISEWGHDF
690
RDSFRKLGSL
700
KTALPMVPIV
710
ALTATASSSI
720
REDIVRCLNL
730
RNPQITCTGF
740
DRPNLYLEVR
750
RKTGNILQDL
760
QPFLVKTSSH
770
WEFEGPTIIY
780
CPSRKMTQQV
790
TGELRKLNLS
800
CGTYHAGMSF
810
STRKDIHHRF
820
VRDEIQCVIA
830
TIAFGMGINK
840
ADIRQVIHYG
850
APKDMESYYQ
860
EIGRAGRDGL
870
QSSCHVLWAP
880
ADINLNRHLL
890
TEIRNEKFRL
900
YKLKMMAKME
910
KYLHSSRCRR
920
QIILSHFEDK
930
QVQKASLGIM
940
GTEKCCDNCR
950
SRLDHCYSMD
960
DSEDTSWDFG
970
PQAFKLLSAV
980
DILGEKFGIG
990
LPILFLRGSN
1000
SQRLADQYRR
1010
HSLFGTGKDQ
1020
TESWWKAFSR
1030
QLITEGFLVE
1040
VSRYNKFMKI
1050
CALTKKGRNW
1060
LHKANTESQS
1070
LILQANEELC
1080
PKKLLLPSSK
1090
TVSSGTKEHC
1100
YNQVPVELST
1110
EKKSNLEKLY
1120
SYKPCDKISS
1130
GSNISKKSIM
1140
VQSPEKAYSS
1150
SQPVISAQEQ
1160
ETQIVLYGKL
1170
VEARQKHANK
1180
MDVPPAILAT
1190
NKILVDMAKM
1200
RPTTVENVKR
1210
IDGVSEGKAA
1220
MLAPLLEVIK
1230
HFCQTNSVQT
1240
DLFSSTKPQE
1250
EQKTSLVAKN
1260
KICTLSQSMA
1270
ITYSLFQEKK
1280
MPLKSIAESR
1290
ILPLMTIGMH
1300
LSQAVKAGCP
1310
LDLERAGLTP
1320
EVQKIIADVI
1330
RNPPVNSDMS
1340
KISLIRMLVP
1350
ENIDTYLIHM
1360
AIEILKHGPD
1370
SGLQPSCDVN
1380
KRRCFPGSEE
1390
ICSSSKRSKE
1400
EVGINTETSS
1410
AERKRRLPVW
1420
FAKGSDTSKK
1430
LMDKTKRGGL
FS
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005813 |
centrosome |
| Biological Process |
GO:0061820 |
telomeric D-loop disassembly |
| Cellular Component |
GO:0005694 |
chromosome |
| Cellular Component |
GO:0000781 |
chromosome, telomeric region |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0016607 |
nuclear speck |
| Cellular Component |
GO:0005730 |
nucleolus |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0005657 |
replication fork |
| Molecular Function |
GO:0043138 |
3'-5' DNA helicase activity |
| Molecular Function |
GO:0008408 |
3'-5' exonuclease activity |
| Molecular Function |
GO:0070337 |
3'-flap-structured DNA binding |
| Molecular Function |
GO:1905773 |
8-hydroxy-2'-deoxyguanosine DNA binding |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0016887 |
ATP hydrolysis activity |
| Molecular Function |
GO:0000405 |
bubble DNA binding |
| Molecular Function |
GO:0003677 |
DNA binding |
| Molecular Function |
GO:0003678 |
DNA helicase activity |
| Molecular Function |
GO:0004527 |
exonuclease activity |
| Molecular Function |
GO:0061749 |
forked DNA-dependent helicase activity |
| Molecular Function |
GO:0000400 |
four-way junction DNA binding |
| Molecular Function |
GO:0009378 |
four-way junction helicase activity |
| Molecular Function |
GO:0051880 |
G-quadruplex DNA binding |
| Molecular Function |
GO:0000287 |
magnesium ion binding |
| Molecular Function |
GO:0030145 |
manganese ion binding |
| Molecular Function |
GO:0032405 |
MutLalpha complex binding |
| Molecular Function |
GO:0042803 |
protein homodimerization activity |
| Molecular Function |
GO:0044877 |
protein-containing complex binding |
| Molecular Function |
GO:0061821 |
telomeric D-loop binding |
| Molecular Function |
GO:0061849 |
telomeric G-quadruplex DNA binding |
| Molecular Function |
GO:0000403 |
Y-form DNA binding |
| Biological Process |
GO:0006284 |
base-excision repair |
| Biological Process |
GO:0071480 |
cellular response to gamma radiation |
| Biological Process |
GO:0009267 |
cellular response to starvation |
| Biological Process |
GO:0090398 |
cellular senescence |
| Biological Process |
GO:0006974 |
DNA damage response |
| Biological Process |
GO:0032392 |
DNA geometric change |
| Biological Process |
GO:0006259 |
DNA metabolic process |
| Biological Process |
GO:0006260 |
DNA replication |
| Biological Process |
GO:0000731 |
DNA synthesis involved in DNA repair |
| Biological Process |
GO:0006302 |
double-strand break repair |
| Biological Process |
GO:0000724 |
double-strand break repair via homologous recombination |
| Biological Process |
GO:0006298 |
mismatch repair |
| Biological Process |
GO:0098530 |
positive regulation of strand invasion |
| Biological Process |
GO:1902570 |
protein localization to nucleolus |
| Biological Process |
GO:0031297 |
replication fork processing |
| Biological Process |
GO:0010225 |
response to UV-C |
| Biological Process |
GO:0090656 |
t-circle formation |
| Biological Process |
GO:0000723 |
telomere maintenance |
| Biological Process |
GO:0032201 |
telomere maintenance via semi-conservative replication |
Reference
[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.