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Q14191

- WRN_HUMAN

UniProt

Q14191 - WRN_HUMAN

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Protein

Werner syndrome ATP-dependent helicase

Gene

WRN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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). Plays a role in double-strand break repair after gamma-irradiation.By similarity6 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.1 Publication

Cofactori

Mg2+1 Publication, Mn2+1 Publication, Zn2+1 PublicationNote: Binds 2 magnesium ions per subunit. Has high activity with manganese and zinc ions (in vitro).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi82 – 821Magnesium 1; catalytic
Metal bindingi82 – 821Magnesium 2; catalytic
Metal bindingi84 – 841Magnesium 1; catalytic
Sitei145 – 1451Interaction with DNACurated
Metal bindingi216 – 2161Magnesium 1; catalytic
Sitei1037 – 10371Interaction with DNA

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi571 – 5788ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. 3'-5' DNA helicase activity Source: UniProtKB
  2. 3'-5' exonuclease activity Source: UniProtKB
  3. ATPase activity Source: UniProtKB
  4. ATP binding Source: UniProtKB-KW
  5. ATP-dependent 3'-5' DNA helicase activity Source: InterPro
  6. ATP-dependent DNA helicase activity Source: UniProtKB
  7. bubble DNA binding Source: UniProtKB
  8. DNA binding Source: UniProtKB
  9. DNA helicase activity Source: UniProtKB
  10. exonuclease activity Source: MGI
  11. four-way junction helicase activity Source: UniProtKB
  12. G-quadruplex DNA binding Source: UniProtKB
  13. helicase activity Source: UniProtKB
  14. magnesium ion binding Source: UniProtKB
  15. manganese ion binding Source: UniProtKB
  16. protein complex binding Source: UniProtKB
  17. protein homodimerization activity Source: UniProtKB
  18. Y-form DNA binding Source: UniProtKB

GO - Biological processi

  1. aging Source: UniProtKB
  2. ATP catabolic process Source: GOC
  3. base-excision repair Source: UniProtKB
  4. cell aging Source: UniProtKB
  5. cellular response to DNA damage stimulus Source: UniProtKB
  6. cellular response to gamma radiation Source: UniProtKB
  7. cellular response to starvation Source: MGI
  8. DNA duplex unwinding Source: GOC
  9. DNA metabolic process Source: UniProtKB
  10. DNA recombination Source: InterPro
  11. DNA replication Source: UniProtKB
  12. DNA synthesis involved in DNA repair Source: UniProtKB
  13. double-strand break repair Source: UniProtKB
  14. multicellular organismal aging Source: UniProtKB
  15. nucleic acid phosphodiester bond hydrolysis Source: GOC
  16. nucleolus to nucleoplasm transport Source: MGI
  17. positive regulation of hydrolase activity Source: UniProtKB
  18. regulation of apoptotic process Source: MGI
  19. regulation of growth rate Source: Ensembl
  20. replication fork processing Source: UniProtKB
  21. replicative cell aging Source: Ensembl
  22. response to oxidative stress Source: UniProtKB
  23. response to UV-C Source: UniProtKB
  24. telomere maintenance Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Helicase, Hydrolase, Nuclease

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, DNA-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Werner syndrome ATP-dependent helicase (EC:3.6.4.12)
Alternative name(s):
DNA helicase, RecQ-like type 3
Short name:
RecQ3
Exonuclease WRN (EC:3.1.-.-)
RecQ protein-like 2
Gene namesi
Name:WRN
Synonyms:RECQ3, RECQL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:12791. WRN.

Subcellular locationi

Nucleusnucleolus. Nucleus. Nucleusnucleoplasm
Note: Gamma-irradiation leads to its translocation from nucleoli to nucleoplasm and PML regulates the irradiation-induced WRN relocation.

GO - Cellular componenti

  1. centrosome Source: UniProtKB
  2. nucleolus Source: UniProtKB
  3. nucleoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Werner syndrome (WRN) [MIM:277700]: A rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti125 – 1251K → N in WRN. 1 Publication
VAR_026588
Natural varianti135 – 1351K → E in WRN. 1 Publication
VAR_026589
Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Note: The disease may be caused by mutations affecting the gene represented in this entry.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi84 – 841E → A: Abolishes exonuclease activity. 2 Publications
Mutagenesisi88 – 881L → A: No effect on exonuclease activity.
Mutagenesisi145 – 1451W → A: Reduces exonuclease activity. 1 Publication
Mutagenesisi212 – 2121Y → F: Strongly reduces exonuclease activity. 1 Publication
Mutagenesisi987 – 9871R → A: Reduces affinity for DNA about 8-fold. Loss of DNA binding; when associated with A-993. 1 Publication
Mutagenesisi989 – 9891S → A: Reduces affinity for DNA about 4-fold. 1 Publication
Mutagenesisi993 – 9931R → A: Reduces affinity for DNA about 20-fold. Loss of DNA binding; when associated with A-987. 1 Publication
Mutagenesisi993 – 9931R → E: Loss of DNA binding. 1 Publication
Mutagenesisi1037 – 10371F → A: Reduces affinity for DNA about 8-fold. 1 Publication
Mutagenesisi1038 – 10381M → A: Reduces affinity for DNA about 4-fold. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi114500. phenotype.
277700. phenotype.
Orphaneti902. Werner syndrome.
PharmGKBiPA367.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 14321431Werner syndrome ATP-dependent helicasePRO_0000205045Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication
Modified residuei426 – 4261Phosphoserine1 Publication
Modified residuei440 – 4401Phosphoserine2 Publications
Modified residuei453 – 4531Phosphoserine1 Publication
Modified residuei467 – 4671Phosphoserine2 Publications
Modified residuei1133 – 11331Phosphoserine1 Publication

Post-translational modificationi

Phosphorylated by PRKDC.4 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ14191.
PaxDbiQ14191.
PRIDEiQ14191.

PTM databases

PhosphoSiteiQ14191.

Expressioni

Gene expression databases

BgeeiQ14191.
CleanExiHS_WRN.
GenevestigatoriQ14191.

Organism-specific databases

HPAiHPA028661.

Interactioni

Subunit structurei

Monomer, and homooligomer. May exist as homodimer, homotrimer, homotetramer and/or homohexamer. Homotetramer, or homohexamer, when bound to DNA. Interacts via its N-terminal domain with WRNIP1 (By similarity). Interacts with EXO1, PCNA and SUPV3L1. Interacts with PML (isoform PML-4).By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BLMP541329EBI-368417,EBI-621372
FEN1P397489EBI-368417,EBI-707816
PARP1P098748EBI-368417,EBI-355676
RAD52P433519EBI-368417,EBI-706448
RPA1P276948EBI-368417,EBI-621389
SIRT1Q96EB69EBI-368417,EBI-1802965
TERF2Q155548EBI-368417,EBI-706637
TP53P046375EBI-368417,EBI-366083
XRCC6P129564EBI-368417,EBI-353208

Protein-protein interaction databases

BioGridi113323. 45 interactions.
DIPiDIP-31380N.
IntActiQ14191. 20 interactions.
MINTiMINT-95856.
STRINGi9606.ENSP00000298139.

Structurei

Secondary structure

1
1432
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi39 – 413Combined sources
Beta strandi51 – 566Combined sources
Helixi59 – 7214Combined sources
Beta strandi78 – 847Combined sources
Beta strandi99 – 1057Combined sources
Beta strandi108 – 1125Combined sources
Helixi114 – 1163Combined sources
Beta strandi117 – 1193Combined sources
Helixi122 – 1287Combined sources
Beta strandi133 – 1397Combined sources
Helixi140 – 15112Combined sources
Beta strandi157 – 1604Combined sources
Helixi161 – 1699Combined sources
Helixi177 – 1859Combined sources
Helixi193 – 1964Combined sources
Beta strandi202 – 2043Combined sources
Helixi207 – 22822Combined sources
Beta strandi955 – 9584Combined sources
Helixi960 – 97213Combined sources
Turni973 – 9753Combined sources
Helixi980 – 9867Combined sources
Helixi996 – 10005Combined sources
Turni1002 – 10098Combined sources
Helixi1012 – 102413Combined sources
Beta strandi1027 – 10326Combined sources
Turni1036 – 10383Combined sources
Beta strandi1039 – 10435Combined sources
Helixi1045 – 105410Combined sources
Beta strandi1062 – 10643Combined sources
Helixi1147 – 117125Combined sources
Helixi1175 – 11784Combined sources
Helixi1181 – 119010Combined sources
Helixi1195 – 11984Combined sources
Beta strandi1201 – 12033Combined sources
Helixi1206 – 12116Combined sources
Helixi1213 – 122513Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2AXLNMR-A949-1092[»]
2DGZNMR-A1140-1239[»]
2E1EX-ray2.30A1142-1242[»]
2E1FX-ray2.00A1142-1242[»]
2FBTX-ray2.05A38-236[»]
2FBVX-ray2.40A38-236[»]
2FBXX-ray2.20A38-236[»]
2FBYX-ray2.00A38-236[»]
2FC0X-ray2.00A38-236[»]
3AAFX-ray1.90A/B949-1079[»]
DisProtiDP00443.
ProteinModelPortaliQ14191.
SMRiQ14191. Positions 38-231, 540-1092, 1142-1235.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14191.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini60 – 2281693'-5' exonucleaseAdd
BLAST
Repeati424 – 4502711 PublicationAdd
BLAST
Repeati451 – 4772721 PublicationAdd
BLAST
Domaini558 – 724167Helicase ATP-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini749 – 899151Helicase C-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini1150 – 122980HRDCPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 277276Interaction with WRNIP1By similarityAdd
BLAST
Regioni424 – 477542 X 27 AA tandem repeats of H-L-S-P-N-D-N-E-N-D-T-S-Y-V-I-E-S-D-E-D-L-E-M-E-M-L-KAdd
BLAST
Regioni987 – 9937Interaction with DNA

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi668 – 6714DEAH box

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi507 – 5104Poly-Glu

Sequence similaritiesi

Belongs to the helicase family. RecQ subfamily.Curated
Contains 1 3'-5' exonuclease domain.Curated
Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
Contains 1 helicase C-terminal domain.PROSITE-ProRule annotation
Contains 1 HRDC domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG0514.
GeneTreeiENSGT00550000074520.
HOGENOMiHOG000146447.
HOVERGENiHBG000325.
InParanoidiQ14191.
KOiK10900.
OMAiGIEGDQW.
OrthoDBiEOG7J70F2.
PhylomeDBiQ14191.
TreeFamiTF312852.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
1.10.150.80. 1 hit.
3.30.420.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR002562. 3'-5'_exonuclease_dom.
IPR011545. DEAD/DEAH_box_helicase_dom.
IPR004589. DNA_helicase_ATP-dep_RecQ.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR029491. Helicase_HTH.
IPR010997. HRDC-like.
IPR002121. HRDC_dom.
IPR027417. P-loop_NTPase.
IPR012337. RNaseH-like_dom.
IPR018982. RQC_domain.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00270. DEAD. 1 hit.
PF01612. DNA_pol_A_exo1. 1 hit.
PF00271. Helicase_C. 1 hit.
PF00570. HRDC. 1 hit.
PF14493. HTH_40. 1 hit.
PF09382. RQC. 1 hit.
[Graphical view]
SMARTiSM00474. 35EXOc. 1 hit.
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SM00341. HRDC. 1 hit.
SM00956. RQC. 1 hit.
[Graphical view]
SUPFAMiSSF47819. SSF47819. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53098. SSF53098. 1 hit.
TIGRFAMsiTIGR00614. recQ_fam. 1 hit.
PROSITEiPS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS50967. HRDC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q14191-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSEKKLETTA QQRKCPEWMN VQNKRCAVEE RKACVRKSVF EDDLPFLEFT
60 70 80 90 100
GSIVYSYDAS DCSFLSEDIS MSLSDGDVVG FDMEWPPLYN RGKLGKVALI
110 120 130 140 150
QLCVSESKCY LFHVSSMSVF PQGLKMLLEN KAVKKAGVGI EGDQWKLLRD
160 170 180 190 200
FDIKLKNFVE LTDVANKKLK CTETWSLNSL VKHLLGKQLL KDKSIRCSNW
210 220 230 240 250
SKFPLTEDQK LYAATDAYAG FIIYRNLEIL DDTVQRFAIN KEEEILLSDM
260 270 280 290 300
NKQLTSISEE VMDLAKHLPH AFSKLENPRR VSILLKDISE NLYSLRRMII
310 320 330 340 350
GSTNIETELR PSNNLNLLSF EDSTTGGVQQ KQIREHEVLI HVEDETWDPT
360 370 380 390 400
LDHLAKHDGE DVLGNKVERK EDGFEDGVED NKLKENMERA CLMSLDITEH
410 420 430 440 450
ELQILEQQSQ EEYLSDIAYK STEHLSPNDN ENDTSYVIES DEDLEMEMLK
460 470 480 490 500
HLSPNDNEND TSYVIESDED LEMEMLKSLE NLNSGTVEPT HSKCLKMERN
510 520 530 540 550
LGLPTKEEEE DDENEANEGE EDDDKDFLWP APNEEQVTCL KMYFGHSSFK
560 570 580 590 600
PVQWKVIHSV LEERRDNVAV MATGYGKSLC FQYPPVYVGK IGLVISPLIS
610 620 630 640 650
LMEDQVLQLK MSNIPACFLG SAQSENVLTD IKLGKYRIVY VTPEYCSGNM
660 670 680 690 700
GLLQQLEADI GITLIAVDEA HCISEWGHDF RDSFRKLGSL KTALPMVPIV
710 720 730 740 750
ALTATASSSI REDIVRCLNL RNPQITCTGF DRPNLYLEVR RKTGNILQDL
760 770 780 790 800
QPFLVKTSSH WEFEGPTIIY CPSRKMTQQV TGELRKLNLS CGTYHAGMSF
810 820 830 840 850
STRKDIHHRF VRDEIQCVIA TIAFGMGINK ADIRQVIHYG APKDMESYYQ
860 870 880 890 900
EIGRAGRDGL QSSCHVLWAP ADINLNRHLL TEIRNEKFRL YKLKMMAKME
910 920 930 940 950
KYLHSSRCRR QIILSHFEDK QVQKASLGIM GTEKCCDNCR SRLDHCYSMD
960 970 980 990 1000
DSEDTSWDFG PQAFKLLSAV DILGEKFGIG LPILFLRGSN SQRLADQYRR
1010 1020 1030 1040 1050
HSLFGTGKDQ TESWWKAFSR QLITEGFLVE VSRYNKFMKI CALTKKGRNW
1060 1070 1080 1090 1100
LHKANTESQS LILQANEELC PKKLLLPSSK TVSSGTKEHC YNQVPVELST
1110 1120 1130 1140 1150
EKKSNLEKLY SYKPCDKISS GSNISKKSIM VQSPEKAYSS SQPVISAQEQ
1160 1170 1180 1190 1200
ETQIVLYGKL VEARQKHANK MDVPPAILAT NKILVDMAKM RPTTVENVKR
1210 1220 1230 1240 1250
IDGVSEGKAA MLAPLLEVIK HFCQTNSVQT DLFSSTKPQE EQKTSLVAKN
1260 1270 1280 1290 1300
KICTLSQSMA ITYSLFQEKK MPLKSIAESR ILPLMTIGMH LSQAVKAGCP
1310 1320 1330 1340 1350
LDLERAGLTP EVQKIIADVI RNPPVNSDMS KISLIRMLVP ENIDTYLIHM
1360 1370 1380 1390 1400
AIEILKHGPD SGLQPSCDVN KRRCFPGSEE ICSSSKRSKE EVGINTETSS
1410 1420 1430
AERKRRLPVW FAKGSDTSKK LMDKTKRGGL FS
Length:1,432
Mass (Da):162,461
Last modified:February 8, 2011 - v2
Checksum:i63F10D19E90AA461
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti32 – 321K → R.1 Publication
Corresponds to variant rs34477820 [ dbSNP | Ensembl ].
VAR_017453
Natural varianti92 – 921G → V in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036318
Natural varianti114 – 1141V → I No effect on exonuclease activity. 2 Publications
Corresponds to variant rs2230009 [ dbSNP | Ensembl ].
VAR_017454
Natural varianti125 – 1251K → N in WRN. 1 Publication
VAR_026588
Natural varianti135 – 1351K → E in WRN. 1 Publication
VAR_026589
Natural varianti172 – 1721T → P No effect on exonuclease activity. 1 Publication
VAR_017455
Natural varianti240 – 2401N → K.1 Publication
Corresponds to variant rs148229804 [ dbSNP | Ensembl ].
VAR_017456
Natural varianti324 – 3241T → A.1 Publication
Corresponds to variant rs1800390 [ dbSNP | Ensembl ].
VAR_006904
Natural varianti329 – 3291Q → R.
Corresponds to variant rs4987237 [ dbSNP | Ensembl ].
VAR_020450
Natural varianti343 – 3431E → K.1 Publication
Corresponds to variant rs11574222 [ dbSNP | Ensembl ].
VAR_018941
Natural varianti383 – 3831L → F.
Corresponds to variant rs4987238 [ dbSNP | Ensembl ].
VAR_020451
Natural varianti383 – 3831L → W.1 Publication
VAR_017457
Natural varianti387 – 3871M → I.4 Publications
Corresponds to variant rs1800391 [ dbSNP | Ensembl ].
VAR_006905
Natural varianti533 – 5331N → S.1 Publication
Corresponds to variant rs11574240 [ dbSNP | Ensembl ].
VAR_018942
Natural varianti612 – 6121S → C.1 Publication
Corresponds to variant rs11574250 [ dbSNP | Ensembl ].
VAR_018943
Natural varianti708 – 7081S → F.1 Publication
Corresponds to variant rs11574289 [ dbSNP | Ensembl ].
VAR_018944
Natural varianti711 – 7111R → W.
Corresponds to variant rs34560788 [ dbSNP | Ensembl ].
VAR_057124
Natural varianti724 – 7241Q → L.1 Publication
VAR_017458
Natural varianti834 – 8341R → C.1 Publication
Corresponds to variant rs3087425 [ dbSNP | Ensembl ].
VAR_014913
Natural varianti912 – 9121I → S.1 Publication
Corresponds to variant rs11574323 [ dbSNP | Ensembl ].
VAR_018945
Natural varianti1074 – 10741L → F.5 Publications
Corresponds to variant rs1801195 [ dbSNP | Ensembl ].
VAR_007903
Natural varianti1079 – 10791S → L.1 Publication
Corresponds to variant rs3087414 [ dbSNP | Ensembl ].
VAR_014914
Natural varianti1133 – 11331S → A.1 Publication
Corresponds to variant rs11574358 [ dbSNP | Ensembl ].
VAR_018946
Natural varianti1141 – 11411S → L.1 Publication
VAR_054162
Natural varianti1269 – 12691K → E.1 Publication
VAR_017459
Natural varianti1339 – 13391V → I.1 Publication
Corresponds to variant rs11574395 [ dbSNP | Ensembl ].
VAR_018947
Natural varianti1367 – 13671C → R Polymorphism associated with a higher risk of myocardial infarction. 4 Publications
Corresponds to variant rs1346044 [ dbSNP | Ensembl ].
VAR_006906

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76937 Genomic DNA. Translation: AAC41981.1.
AY818673 mRNA. Translation: AAX21098.1.
AF091214 mRNA. Translation: AAC63361.1.
AF181897, AF181896 Genomic DNA. Translation: AAF06162.1.
AY442327 Genomic DNA. Translation: AAR05448.1.
AC084736 Genomic DNA. No translation available.
CCDSiCCDS6082.1.
RefSeqiNP_000544.2. NM_000553.4.
UniGeneiHs.632050.

Genome annotation databases

EnsembliENST00000298139; ENSP00000298139; ENSG00000165392.
GeneIDi7486.
KEGGihsa:7486.
UCSCiuc003xio.4. human.

Polymorphism databases

DMDMi322510082.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

WRN

WRN mutation db (Warner disease)

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76937 Genomic DNA. Translation: AAC41981.1 .
AY818673 mRNA. Translation: AAX21098.1 .
AF091214 mRNA. Translation: AAC63361.1 .
AF181897 , AF181896 Genomic DNA. Translation: AAF06162.1 .
AY442327 Genomic DNA. Translation: AAR05448.1 .
AC084736 Genomic DNA. No translation available.
CCDSi CCDS6082.1.
RefSeqi NP_000544.2. NM_000553.4.
UniGenei Hs.632050.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2AXL NMR - A 949-1092 [» ]
2DGZ NMR - A 1140-1239 [» ]
2E1E X-ray 2.30 A 1142-1242 [» ]
2E1F X-ray 2.00 A 1142-1242 [» ]
2FBT X-ray 2.05 A 38-236 [» ]
2FBV X-ray 2.40 A 38-236 [» ]
2FBX X-ray 2.20 A 38-236 [» ]
2FBY X-ray 2.00 A 38-236 [» ]
2FC0 X-ray 2.00 A 38-236 [» ]
3AAF X-ray 1.90 A/B 949-1079 [» ]
DisProti DP00443.
ProteinModelPortali Q14191.
SMRi Q14191. Positions 38-231, 540-1092, 1142-1235.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113323. 45 interactions.
DIPi DIP-31380N.
IntActi Q14191. 20 interactions.
MINTi MINT-95856.
STRINGi 9606.ENSP00000298139.

Chemistry

BindingDBi Q14191.
ChEMBLi CHEMBL2146312.

PTM databases

PhosphoSitei Q14191.

Polymorphism databases

DMDMi 322510082.

Proteomic databases

MaxQBi Q14191.
PaxDbi Q14191.
PRIDEi Q14191.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000298139 ; ENSP00000298139 ; ENSG00000165392 .
GeneIDi 7486.
KEGGi hsa:7486.
UCSCi uc003xio.4. human.

Organism-specific databases

CTDi 7486.
GeneCardsi GC08P030948.
GeneReviewsi WRN.
H-InvDB HIX0007441.
HGNCi HGNC:12791. WRN.
HPAi HPA028661.
MIMi 114500. phenotype.
277700. phenotype.
604611. gene.
neXtProti NX_Q14191.
Orphaneti 902. Werner syndrome.
PharmGKBi PA367.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0514.
GeneTreei ENSGT00550000074520.
HOGENOMi HOG000146447.
HOVERGENi HBG000325.
InParanoidi Q14191.
KOi K10900.
OMAi GIEGDQW.
OrthoDBi EOG7J70F2.
PhylomeDBi Q14191.
TreeFami TF312852.

Miscellaneous databases

ChiTaRSi WRN. human.
EvolutionaryTracei Q14191.
GeneWikii Werner_syndrome_ATP-dependent_helicase.
GenomeRNAii 7486.
NextBioi 29326.
PROi Q14191.
SOURCEi Search...

Gene expression databases

Bgeei Q14191.
CleanExi HS_WRN.
Genevestigatori Q14191.

Family and domain databases

Gene3Di 1.10.10.10. 1 hit.
1.10.150.80. 1 hit.
3.30.420.10. 1 hit.
3.40.50.300. 2 hits.
InterProi IPR002562. 3'-5'_exonuclease_dom.
IPR011545. DEAD/DEAH_box_helicase_dom.
IPR004589. DNA_helicase_ATP-dep_RecQ.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR029491. Helicase_HTH.
IPR010997. HRDC-like.
IPR002121. HRDC_dom.
IPR027417. P-loop_NTPase.
IPR012337. RNaseH-like_dom.
IPR018982. RQC_domain.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view ]
Pfami PF00270. DEAD. 1 hit.
PF01612. DNA_pol_A_exo1. 1 hit.
PF00271. Helicase_C. 1 hit.
PF00570. HRDC. 1 hit.
PF14493. HTH_40. 1 hit.
PF09382. RQC. 1 hit.
[Graphical view ]
SMARTi SM00474. 35EXOc. 1 hit.
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SM00341. HRDC. 1 hit.
SM00956. RQC. 1 hit.
[Graphical view ]
SUPFAMi SSF47819. SSF47819. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53098. SSF53098. 1 hit.
TIGRFAMsi TIGR00614. recQ_fam. 1 hit.
PROSITEi PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS50967. HRDC. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PHE-1074.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PHE-1074.
  3. "Genomic structure of the human Werner's gene and cloning of the mouse homolog."
    Paeper B.W., Gayle M., Brady W., Swartz A., Gillett L.A., Alisch R.S., Mulligan J., Galas D., Fu Y.-H.
    Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PHE-1074.
  4. NIEHS SNPs program
    Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-114; LYS-343; ILE-387; SER-533; CYS-612; PHE-708; CYS-834; SER-912; LEU-1079; ALA-1133; ILE-1339 AND ARG-1367.
  5. "DNA sequence and analysis of human chromosome 8."
    Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T.
    , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
    Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "Nucleolar localization of the Werner syndrome protein in human cells."
    Marciniak R.A., Lombard D.B., Johnson F.B., Guarente L.
    Proc. Natl. Acad. Sci. U.S.A. 95:6887-6892(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  7. "Evolution of the RECQ family of helicases: a Drosophila homolog, Dmblm, is similar to the human Bloom syndrome gene."
    Kusano K., Berres M.E., Engels W.R.
    Genetics 151:1027-1039(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: REPEATS.
  8. "A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3'- 5' exonuclease and 5'-protruding strand endonuclease activities."
    Xue Y., Ratcliff G.C., Wang H., Davis-Searles P.R., Gray M.D., Erie D.A., Redinbo M.R.
    Biochemistry 41:2901-2912(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF GLU-84, FUNCTION AS AN EXONUCLEASE, DNA-BINDING, INTERACTION WITH PCNA, SUBUNIT.
  9. "Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation."
    Karmakar P., Piotrowski J., Brosh R.M. Jr., Sommers J.A., Miller S.P., Cheng W.H., Snowden C.M., Ramsden D.A., Bohr V.A.
    J. Biol. Chem. 277:18291-18302(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  10. "The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein."
    Sharma S., Sommers J.A., Driscoll H.C., Uzdilla L.A., Wilson T.M., Brosh R.M. Jr.
    J. Biol. Chem. 278:23487-23496(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EXO1.
  11. "Interaction of human SUV3 RNA/DNA helicase with BLM helicase; loss of the SUV3 gene results in mouse embryonic lethality."
    Pereira M., Mason P., Szczesny R.J., Maddukuri L., Dziwura S., Jedrzejczak R., Paul E., Wojcik A., Dybczynska L., Tudek B., Bartnik E., Klysik J., Bohr V.A., Stepien P.P.
    Mech. Ageing Dev. 128:609-617(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SUPV3L1.
  12. "Werner syndrome protein interacts functionally with translesion DNA polymerases."
    Kamath-Loeb A.S., Lan L., Nakajima S., Yasui A., Loeb L.A.
    Proc. Natl. Acad. Sci. U.S.A. 104:10394-10399(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic kidney.
  14. "The Werner syndrome protein binds replication fork and Holliday junction DNAs as an oligomer."
    Compton S.A., Tolun G., Kamath-Loeb A.S., Loeb L.A., Griffith J.D.
    J. Biol. Chem. 283:24478-24483(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, DNA-BINDING.
  15. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-440 AND SER-467, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  16. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  17. "WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts."
    Zecevic A., Menard H., Gurel V., Hagan E., DeCaro R., Zhitkovich A.
    Cell Cycle 8:2769-2778(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  18. "The Werner syndrome helicase/exonuclease processes mobile D-loops through branch migration and degradation."
    Opresko P.L., Sowd G., Wang H.
    PLoS ONE 4:E4825-E4825(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  19. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-426; SER-440; SER-453 AND SER-467, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  20. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  21. "Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in gamma-irradiation-induced DNA damage responses."
    Liu J., Song Y., Qian J., Liu B., Dong Y., Tian B., Sun Z.
    Biochemistry (Mosc.) 76:550-554(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PML.
  22. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1133, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  23. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  24. "Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein."
    Hu J.S., Feng H., Zeng W., Lin G.X., Xi X.G.
    Proc. Natl. Acad. Sci. U.S.A. 102:18379-18384(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 949-1092.
  25. "WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing."
    Perry J.J., Yannone S.M., Holden L.G., Hitomi C., Asaithamby A., Han S., Cooper P.K., Chen D.J., Tainer J.A.
    Nat. Struct. Mol. Biol. 13:414-422(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 38-236 IN COMPLEXES WITH MAGNESIUM; MANGANESE; EUROPIUM AND GMP, PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF GLU-84; TRP-145 AND TYR-212, CHARACTERIZATION OF VARIANTS ILE-114 AND PRO-172.
  26. Cited for: REVIEW ON VARIANTS.
  27. "Solution structure of the helicase and RNase D C-terminal domain in Werner syndrome ATP-dependent helicase."
    RIKEN structural genomics initiative (RSGI)
    Submitted (SEP-2006) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 1140-1239.
  28. "Crystal structure of the HRDC domain of human Werner syndrome protein, WRN."
    Kitano K., Yoshihara N., Hakoshima T.
    J. Biol. Chem. 282:2717-2728(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1142-1242, PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, CIRCULAR DICHROISM.
  29. "Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicase WRN."
    Kitano K., Kim S.Y., Hakoshima T.
    Structure 18:177-187(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 949-1079 IN COMPLEX WITH DOUBLE-STRANDED DNA, INTERACTION WITH DNA, MUTAGENESIS OF ARG-987; SER-989; ARG-993; PHE-1037 AND MET-1038.
  30. "Association of a polymorphic variant of the Werner helicase gene with myocardial infarction in a Japanese population."
    Ye L., Miki T., Nakura J., Oshima J., Kamino K., Rakugi H., Ikegami H., Higaki J., Edland S.D., Martin G.M., Ogihara T.
    Am. J. Med. Genet. 68:494-498(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ARG-1367.
  31. "Werner syndrome: characterization of mutations in the WRN gene in an affected family."
    Meisslitzer C., Ruppitsch W., Weirich-Schwaiger H., Weirich H.G., Jabkowsky J., Klein G., Schweiger M., Hirsch-Kauffmann M.
    Eur. J. Hum. Genet. 5:364-370(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ILE-387 AND PHE-1074.
  32. "The 1396del A mutation and a missense mutation or a rare polymorphism of the WRN gene detected in a French Werner family with a severe phenotype and a case of an unusual vulvar cancer."
    Vidal V., Bay J.-O., Champomier F., Grancho M., Beauville L., Glowaczower C., Lemery D., Ferrara M., Bignon Y.-J.
    Hum. Mutat. 11:413-414(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ILE-387.
  33. "Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cys/Arg, and its stability in a population of Finnish centenarians."
    Castro E., Ogburn C.E., Hunt K.E., Tilvis R., Louhija J., Penttinen R., Erkkola R., Panduro A., Riestra R., Piussan C., Deeb S.S., Wang L., Edland S.D., Martin G.M., Oshima J.
    Am. J. Med. Genet. 82:399-403(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ALA-324 AND ARG-1367.
  34. Cited for: VARIANTS ARG-32; ILE-114; PRO-172; LYS-240; TRP-383; ILE-387; LEU-724; PHE-1074; GLU-1269 AND ARG-1367.
  35. Cited for: VARIANTS WRN ASN-125 AND GLU-135.
  36. Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-92.
  37. Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-1141.

Entry informationi

Entry nameiWRN_HUMAN
AccessioniPrimary (citable) accession number: Q14191
Secondary accession number(s): A1KYY9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: February 8, 2011
Last modified: November 26, 2014
This is version 169 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3