WRN_XENLA
ID WRN_XENLA Reviewed; 1436 AA.
AC O93530;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN {ECO:0000305};
DE AltName: Full=Focus-forming activity 1 {ECO:0000303|PubMed:9697700};
DE Short=FFA-1 {ECO:0000303|PubMed:7569932};
DE AltName: Full=Werner syndrome protein homolog {ECO:0000305};
DE Includes:
DE RecName: Full=3'-5' exonuclease;
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q14191};
DE Includes:
DE RecName: Full=ATP-dependent helicase;
DE EC=3.6.4.12 {ECO:0000250|UniProtKB:Q14191};
GN Name=wrn; Synonyms=ffa1;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=9697700; DOI=10.1038/1263;
RA Yan H., Chen C.-Y., Kobayashi R., Newport J.;
RT "Replication focus-forming activity 1 and the Werner syndrome gene
RT product.";
RL Nat. Genet. 19:375-378(1998).
RN [2] {ECO:0000305}
RP FUNCTION.
RX PubMed=7569932; DOI=10.1126/science.7569932;
RA Yan H., Newport J.;
RT "FFA-1, a protein that promotes the formation of replication centers within
RT nuclei.";
RL Science 269:1883-1885(1995).
CC -!- FUNCTION: Multifunctional enzyme that has both magnesium and ATP-
CC dependent DNA-helicase activity and 3'->5' exonuclease activity towards
CC double-stranded DNA with a 5'-overhang. Has no nuclease activity
CC towards single-stranded DNA or blunt-ended double-stranded DNA. Binds
CC preferentially to DNA substrates containing alternate secondary
CC structures, such as replication forks and Holliday junctions. May play
CC an important role in the dissociation of joint DNA molecules that can
CC arise as products of homologous recombination, at stalled replication
CC forks or during DNA repair. Alleviates stalling of DNA polymerases at
CC the site of DNA lesions. Important for genomic integrity. Plays a role
CC in the formation of DNA replication focal centers; stably associates
CC with foci elements generating binding sites for RP-A (By similarity).
CC {ECO:0000250|UniProtKB:Q14191, ECO:0000269|PubMed:7569932,
CC ECO:0000269|PubMed:9697700}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC Evidence={ECO:0000250|UniProtKB:Q14191};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q14191};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q14191};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q14191};
CC Note=Binds 2 magnesium ions per subunit. Has high activity with
CC manganese and zinc ions (in vitro). {ECO:0000250|UniProtKB:Q14191};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q14191}.
CC -!- SIMILARITY: Belongs to the helicase family. RecQ subfamily.
CC {ECO:0000305}.
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DR EMBL; AF067418; AAC63512.1; -; mRNA.
DR PIR; T14895; T14895.
DR RefSeq; NP_001081838.1; NM_001088369.1.
DR AlphaFoldDB; O93530; -.
DR SMR; O93530; -.
DR PRIDE; O93530; -.
DR GeneID; 398079; -.
DR KEGG; xla:398079; -.
DR CTD; 398079; -.
DR Xenbase; XB-GENE-992879; wrn.L.
DR OrthoDB; 445763at2759; -.
DR Proteomes; UP000186698; Chromosome 1L.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0043138; F:3'-5' DNA helicase activity; IEA:InterPro.
DR GO; GO:0008408; F:3'-5' exonuclease activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0006259; P:DNA metabolic process; ISS:UniProtKB.
DR GO; GO:0006310; P:DNA recombination; IEA:InterPro.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IEA:InterPro.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.10.150.80; -; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR002562; 3'-5'_exonuclease_dom.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR004589; DNA_helicase_ATP-dep_RecQ.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR029491; Helicase_HTH.
DR InterPro; IPR010997; HRDC-like_sf.
DR InterPro; IPR002121; HRDC_dom.
DR InterPro; IPR044876; HRDC_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR032284; RecQ_Zn-bd.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR InterPro; IPR018982; RQC_domain.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF01612; DNA_pol_A_exo1; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF00570; HRDC; 1.
DR Pfam; PF14493; HTH_40; 1.
DR Pfam; PF16124; RecQ_Zn_bind; 1.
DR Pfam; PF09382; RQC; 1.
DR SMART; SM00474; 35EXOc; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SMART; SM00341; HRDC; 1.
DR SMART; SM00956; RQC; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF47819; SSF47819; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR TIGRFAMs; TIGR00614; recQ_fam; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS50967; HRDC; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; DNA damage; DNA repair; DNA-binding; Exonuclease; Helicase;
KW Hydrolase; Magnesium; Metal-binding; Multifunctional enzyme; Nuclease;
KW Nucleotide-binding; Nucleus; Reference proteome; Zinc.
FT CHAIN 1..1436
FT /note="Bifunctional 3'-5' exonuclease/ATP-dependent
FT helicase WRN"
FT /id="PRO_0000205047"
FT DOMAIN 51..223
FT /note="3'-5' exonuclease"
FT DOMAIN 499..665
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 690..842
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 1098..1177
FT /note="HRDC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00328"
FT REGION 427..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 930..936
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
FT REGION 1029..1049
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1388..1411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4..16
FT /note="KBM 1"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
FT MOTIF 609..612
FT /note="DEAH box"
FT MOTIF 1401..1410
FT /note="KBM 2"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
FT MOTIF 1422..1436
FT /note="XLM"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
FT COMPBIAS 448..469
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1029..1045
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1388..1402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 76
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
FT BINDING 76
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
FT BINDING 78
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
FT BINDING 210
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
FT BINDING 512..519
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT SITE 139
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
FT SITE 980
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q14191"
SQ SEQUENCE 1436 AA; 161851 MW; 1BEAF05A25B4E230 CRC64;
MTSLQRKLPE WMSVKQQEDR IDDAKKSFCK KNILEDNLPF MKFNGSIVYS YESNDCSLLS
EDIRSSLLEE DVLGFDIEWP PVYTKGKTGK VALIQVCVSE KKCYLFHISP MAGFPKGLKR
LLEDESVRKV GVGIEGDQWK LMSDYELKLK GFIELSEMAN QKLRCKEKWT FNGLIKHLFK
EQLYKRKSYR CSNWDIFLLT EDQKLYAATD AYAGLLIYKK LEGMDAHESD SFRVGREGVA
DCKGVKRQLT DLSKGLMDLV NQVPNSFGCY TEAVRAVDIL EDLSEKLEEL RNIMKEASKA
EGNGLHFQNS EDCSKKDKSI LHVACKESLA EHKMDCKNAD SQNNKDIDSC QNENRDEDFF
MTLGISEEEL YMMEREDDKK QTNPDYKLNK DSCDTNEEKD MSYVIESDED FDSEIIKSLE
DLDNSTEEAL GTGVPQAGLI PAKSVDTVAD EEEDEGIEEE DDDDDWDPSM PEPSAQHISC
LKTYFGHSSF KPVQWKVVHS VLRERRDNLV VMATGYGKSL CYQFAPVYTS GIGIVICPLI
SLMEDQVLQL EMSNISSCFL GSAQSKNVLQ DVKDGKMRVI YMTPEFCSRG ISLLQDLDNR
YGITLIAIDE AHCISEWGHD FRSAYRSLGS LKRMLPNVPI VALTATASPS IREDITKSLN
LHNPQVTCTS FDRPNLYLDV ARKTTNISID LRQFLIKKQQ GSGWEFEGAT IVYCPTRKTS
EQVTAELIKL GIACGTYHAG MGIKQRREVH HRFMRDEIHC VVATVAFGMG INKPDIRKVI
HYGAPKEMES YYQEIGRAGR DGLPSCCHAL WAQADMNFNR HMLGEIPNKG FREYKLKMLT
KMEKYLNSST CRRKIILSHF EDKQLRKASS GIMGTEKCCD NCKTRLICNI SINDTEDNLQ
DFGPQAYKFI SAVDVLGQKF GTGVPVLFLR GSTSQRVPDR FRNHSLFSSG KDQTEAFWKV
LARQLITEGY LQESSGQTKF STICGLTSKG SNWLIKANNE QCPSLLLPSN NELCLQRTRV
SNFSSAQAHS SMVPHASSNT RSSMPKAGPE KMELKDKFSY QEAERLSKAA GVSKSSFKLQ
TPCKLSRPPE PEVSPREREL QTTLYGRLVV ARQKIASERD ILPAVLATNK VLVDMAKLRP
TTSENMKKLD GVSEAKSAML APLLEVVKEF CIANSLKVDV FSGSVSQSES TFFTPREQER
ISLPESQRMS YSLFQEQNLS LKKIADVRCL SMAVVGMHLW QALKAGYSFD VQRAGLTPEM
KKLITYAIKK PPINSDLSSF KAIREYVPAN IDGYPIRMVI SLLEKEGSSG AQGQPEFPTQ
KTLIQTEENP KNVSVQNTKH KVTMGKSMWI EKKPTQPATA ELEVTKGKAL APIMLASWNE
ASLDADTEEL FSESQSSTTR PRRRLPEWFG STKGNAATRC IQESKNLGEE KGSFFD
