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Q14191

- WRN_HUMAN

UniProt

Q14191 - WRN_HUMAN

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
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    • History
      Entry version 167 (01 Oct 2014)
      Sequence version 2 (08 Feb 2011)
      Previous versions | rss
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    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

    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 binding Source: UniProtKB
    17. protein complex binding Source: UniProtKB
    18. protein homodimerization activity Source: UniProtKB
    19. 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

    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

    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 – 4261Phosphoserine2 Publications
    Modified residuei440 – 4401Phosphoserine3 Publications
    Modified residuei453 – 4531Phosphoserine2 Publications
    Modified residuei467 – 4671Phosphoserine3 Publications
    Modified residuei1133 – 11331Phosphoserine2 Publications

    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
    FEN1P3974810EBI-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. 42 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 – 413
    Beta strandi51 – 566
    Helixi59 – 7214
    Beta strandi78 – 847
    Beta strandi99 – 1057
    Beta strandi108 – 1125
    Helixi114 – 1163
    Beta strandi117 – 1193
    Helixi122 – 1287
    Beta strandi133 – 1397
    Helixi140 – 15112
    Beta strandi157 – 1604
    Helixi161 – 1699
    Helixi177 – 1859
    Helixi193 – 1964
    Beta strandi202 – 2043
    Helixi207 – 22822
    Beta strandi955 – 9584
    Helixi960 – 97213
    Turni973 – 9753
    Helixi980 – 9867
    Helixi996 – 10005
    Turni1002 – 10098
    Helixi1012 – 102413
    Beta strandi1027 – 10326
    Turni1036 – 10383
    Beta strandi1039 – 10435
    Helixi1045 – 105410
    Beta strandi1062 – 10643
    Helixi1147 – 117125
    Helixi1175 – 11784
    Helixi1181 – 119010
    Helixi1195 – 11984
    Beta strandi1201 – 12033
    Helixi1206 – 12116
    Helixi1213 – 122513

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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, 532-1235.
    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.
    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. DNA/RNA_helicase_DEAD/DEAH_N.
    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

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    MSEKKLETTA QQRKCPEWMN VQNKRCAVEE RKACVRKSVF EDDLPFLEFT     50
    GSIVYSYDAS DCSFLSEDIS MSLSDGDVVG FDMEWPPLYN RGKLGKVALI 100
    QLCVSESKCY LFHVSSMSVF PQGLKMLLEN KAVKKAGVGI EGDQWKLLRD 150
    FDIKLKNFVE LTDVANKKLK CTETWSLNSL VKHLLGKQLL KDKSIRCSNW 200
    SKFPLTEDQK LYAATDAYAG FIIYRNLEIL DDTVQRFAIN KEEEILLSDM 250
    NKQLTSISEE VMDLAKHLPH AFSKLENPRR VSILLKDISE NLYSLRRMII 300
    GSTNIETELR PSNNLNLLSF EDSTTGGVQQ KQIREHEVLI HVEDETWDPT 350
    LDHLAKHDGE DVLGNKVERK EDGFEDGVED NKLKENMERA CLMSLDITEH 400
    ELQILEQQSQ EEYLSDIAYK STEHLSPNDN ENDTSYVIES DEDLEMEMLK 450
    HLSPNDNEND TSYVIESDED LEMEMLKSLE NLNSGTVEPT HSKCLKMERN 500
    LGLPTKEEEE DDENEANEGE EDDDKDFLWP APNEEQVTCL KMYFGHSSFK 550
    PVQWKVIHSV LEERRDNVAV MATGYGKSLC FQYPPVYVGK IGLVISPLIS 600
    LMEDQVLQLK MSNIPACFLG SAQSENVLTD IKLGKYRIVY VTPEYCSGNM 650
    GLLQQLEADI GITLIAVDEA HCISEWGHDF RDSFRKLGSL KTALPMVPIV 700
    ALTATASSSI REDIVRCLNL RNPQITCTGF DRPNLYLEVR RKTGNILQDL 750
    QPFLVKTSSH WEFEGPTIIY CPSRKMTQQV TGELRKLNLS CGTYHAGMSF 800
    STRKDIHHRF VRDEIQCVIA TIAFGMGINK ADIRQVIHYG APKDMESYYQ 850
    EIGRAGRDGL QSSCHVLWAP ADINLNRHLL TEIRNEKFRL YKLKMMAKME 900
    KYLHSSRCRR QIILSHFEDK QVQKASLGIM GTEKCCDNCR SRLDHCYSMD 950
    DSEDTSWDFG PQAFKLLSAV DILGEKFGIG LPILFLRGSN SQRLADQYRR 1000
    HSLFGTGKDQ TESWWKAFSR QLITEGFLVE VSRYNKFMKI CALTKKGRNW 1050
    LHKANTESQS LILQANEELC PKKLLLPSSK TVSSGTKEHC YNQVPVELST 1100
    EKKSNLEKLY SYKPCDKISS GSNISKKSIM VQSPEKAYSS SQPVISAQEQ 1150
    ETQIVLYGKL VEARQKHANK MDVPPAILAT NKILVDMAKM RPTTVENVKR 1200
    IDGVSEGKAA MLAPLLEVIK HFCQTNSVQT DLFSSTKPQE EQKTSLVAKN 1250
    KICTLSQSMA ITYSLFQEKK MPLKSIAESR ILPLMTIGMH LSQAVKAGCP 1300
    LDLERAGLTP EVQKIIADVI RNPPVNSDMS KISLIRMLVP ENIDTYLIHM 1350
    AIEILKHGPD SGLQPSCDVN KRRCFPGSEE ICSSSKRSKE EVGINTETSS 1400
    AERKRRLPVW FAKGSDTSKK LMDKTKRGGL FS 1432
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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, 532-1235.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113323. 42 interactions.
    DIPi DIP-31380N.
    IntActi Q14191. 20 interactions.
    MINTi MINT-95856.
    STRINGi 9606.ENSP00000298139.

    Chemistry

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

    Miscellaneous databases

    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. DNA/RNA_helicase_DEAD/DEAH_N.
    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

    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: October 1, 2014
    This is version 167 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