HELB_HUMAN
ID HELB_HUMAN Reviewed; 1087 AA.
AC Q8NG08; A8K4C9; Q4G0T2; Q9H7L5;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=DNA helicase B {ECO:0000305};
DE Short=hDHB {ECO:0000303|PubMed:15146062, ECO:0000303|PubMed:22194613};
DE EC=3.6.4.12 {ECO:0000269|PubMed:12181327, ECO:0000305|PubMed:25617833};
GN Name=HELB {ECO:0000312|HGNC:HGNC:17196};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH RPA1, INTERACTION
RP WITH THE DNA POLYMERASE ALPHA COMPLEX, AND MUTAGENESIS OF LYS-481 AND
RP GLU-591.
RX PubMed=12181327; DOI=10.1074/jbc.m208067200;
RA Taneja P., Gu J., Peng R., Carrick R., Uchiumi F., Ott R.D., Gustafson E.,
RA Podust V.N., Fanning E.;
RT "A dominant-negative mutant of human DNA helicase B blocks the onset of
RT chromosomal DNA replication.";
RL J. Biol. Chem. 277:40853-40861(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP PRO-191; LEU-966 AND ILE-980.
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-967, AND MUTAGENESIS OF
RP SER-967; SER-984; SER-1005; SER-1021; 1061-VAL--LEU-1065 AND
RP 1068-LEU--LEU-1070.
RX PubMed=15146062; DOI=10.1091/mbc.e04-03-0227;
RA Gu J., Xia X., Yan P., Liu H., Podust V.N., Reynolds A.B., Fanning E.;
RT "Cell cycle-dependent regulation of a human DNA helicase that localizes in
RT DNA damage foci.";
RL Mol. Biol. Cell 15:3320-3332(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1027, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RPA1, AND MUTAGENESIS OF
RP GLU-499; ASP-506 AND ASP-510.
RX PubMed=22194613; DOI=10.1074/jbc.m111.324582;
RA Guler G.D., Liu H., Vaithiyalingam S., Arnett D.R., Kremmer E.,
RA Chazin W.J., Fanning E.;
RT "Human DNA helicase B (HDHB) binds to replication protein A and facilitates
RT cellular recovery from replication stress.";
RL J. Biol. Chem. 287:6469-6481(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-967 AND SER-1058, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP INTERACTION WITH CDC45 AND TOPB1.
RX PubMed=25933514; DOI=10.1016/j.yexcr.2015.04.014;
RA Gerhardt J., Guler G.D., Fanning E.;
RT "Human DNA helicase B interacts with the replication initiation protein
RT Cdc45 and facilitates Cdc45 binding onto chromatin.";
RL Exp. Cell Res. 334:283-293(2015).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-481 AND GLU-591.
RX PubMed=25617833; DOI=10.1371/journal.pone.0116852;
RA Liu H., Yan P., Fanning E.;
RT "Human DNA helicase B functions in cellular homologous recombination and
RT stimulates Rad51-mediated 5'-3' heteroduplex extension in vitro.";
RL PLoS ONE 10:E0116852-E0116852(2015).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RPA1, AND MUTAGENESIS OF
RP LYS-481; GLU-499; ASP-506; ASP-510 AND GLU-591.
RX PubMed=26774285; DOI=10.1016/j.molcel.2015.12.013;
RA Tkac J., Xu G., Adhikary H., Young J.T., Gallo D., Escribano-Diaz C.,
RA Krietsch J., Orthwein A., Munro M., Sol W., Al-Hakim A., Lin Z.Y.,
RA Jonkers J., Borst P., Brown G.W., Gingras A.C., Rottenberg S., Masson J.Y.,
RA Durocher D.;
RT "HELB is a feedback inhibitor of DNA end resection.";
RL Mol. Cell 61:405-418(2016).
CC -!- FUNCTION: 5'-3' DNA helicase involved in DNA damage response by acting
CC as an inhibitor of DNA end resection (PubMed:25617833,
CC PubMed:26774285). Recruitment to single-stranded DNA (ssDNA) following
CC DNA damage leads to inhibit the nucleases catalyzing resection, such as
CC EXO1, BLM and DNA2, possibly via the 5'-3' ssDNA translocase activity
CC of HELB (PubMed:26774285). As cells approach S phase, DNA end resection
CC is promoted by the nuclear export of HELB following phosphorylation
CC (PubMed:26774285). Acts independently of TP53BP1 (PubMed:26774285).
CC Unwinds duplex DNA with 5'-3' polarity. Has single-strand DNA-dependent
CC ATPase and DNA helicase activities. Prefers ATP and dATP as substrates
CC (PubMed:12181327). During S phase, may facilitate cellular recovery
CC from replication stress (PubMed:22194613).
CC {ECO:0000269|PubMed:12181327, ECO:0000269|PubMed:22194613,
CC ECO:0000269|PubMed:25617833, ECO:0000269|PubMed:26774285}.
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:0000269|PubMed:12181327, ECO:0000305|PubMed:25617833};
CC -!- ACTIVITY REGULATION: Inhibited by salt concentration greater than 100
CC mM. Uses either magnesium or manganese ions to support helicase
CC activity. Binds strongly to single-stranded DNA in the absence of ATP
CC but dissociates readily in the presence of 1 mM ATP.
CC {ECO:0000269|PubMed:12181327}.
CC -!- SUBUNIT: Binds to RPA1; this interaction promotes HELB recruitment to
CC chromatin following DNA damage (PubMed:12181327, PubMed:22194613,
CC PubMed:26774285). Interacts with at least two subunits of the DNA
CC polymerase alpha complex (PubMed:12181327): Interacts with CDC45
CC (PubMed:25933514). Interacts with TOPB1 (PubMed:25933514).
CC {ECO:0000269|PubMed:12181327, ECO:0000269|PubMed:22194613,
CC ECO:0000269|PubMed:25933514}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15146062}. Cytoplasm
CC {ECO:0000269|PubMed:15146062}. Chromosome
CC {ECO:0000269|PubMed:26774285}. Note=Predominantly nuclear
CC (PubMed:15146062). Phosphorylation at Ser-967 by CDK2 during the G1/S
CC transition results in its nuclear export into the cytoplasm as cells
CC approach and progress through S phase (PubMed:15146062). Following DNA
CC damage, recruited to sites of double-strand breaks by the RPA complex
CC (PubMed:26774285). Recruited to chromatin following DNA damage induced
CC by UV irradiation, or camptothecin or hydroxyurea treatment
CC (PubMed:22194613). {ECO:0000269|PubMed:15146062,
CC ECO:0000269|PubMed:22194613, ECO:0000269|PubMed:26774285}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NG08-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NG08-2; Sequence=VSP_034086, VSP_034087;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis and thymus and weakly in
CC liver, spleen, kidney and brain. {ECO:0000269|PubMed:12181327}.
CC -!- PTM: Phosphorylated at Ser-967 by CDK2 during the G1/S transition,
CC resulting in its nuclear export into the cytoplasm (PubMed:15146062,
CC PubMed:26774285). As S phase progresses, its exclusion from the nucleus
CC promotes the activation of long-range resection (PubMed:26774285).
CC {ECO:0000269|PubMed:15146062, ECO:0000269|PubMed:26774285}.
CC -!- SIMILARITY: Belongs to the RecD family. HELB subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15754.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF319995; AAM73554.1; -; mRNA.
DR EMBL; AK024464; BAB15754.1; ALT_INIT; mRNA.
DR EMBL; AK290894; BAF83583.1; -; mRNA.
DR CCDS; CCDS8976.1; -. [Q8NG08-1]
DR RefSeq; NP_387467.2; NM_033647.4. [Q8NG08-1]
DR RefSeq; XP_005269291.1; XM_005269234.2.
DR AlphaFoldDB; Q8NG08; -.
DR BioGRID; 124978; 17.
DR IntAct; Q8NG08; 9.
DR MINT; Q8NG08; -.
DR STRING; 9606.ENSP00000247815; -.
DR iPTMnet; Q8NG08; -.
DR PhosphoSitePlus; Q8NG08; -.
DR BioMuta; HELB; -.
DR DMDM; 190359604; -.
DR EPD; Q8NG08; -.
DR jPOST; Q8NG08; -.
DR MassIVE; Q8NG08; -.
DR MaxQB; Q8NG08; -.
DR PaxDb; Q8NG08; -.
DR PeptideAtlas; Q8NG08; -.
DR PRIDE; Q8NG08; -.
DR ProteomicsDB; 73405; -. [Q8NG08-1]
DR ProteomicsDB; 73406; -. [Q8NG08-2]
DR Antibodypedia; 16658; 33 antibodies from 17 providers.
DR DNASU; 92797; -.
DR Ensembl; ENST00000247815.9; ENSP00000247815.5; ENSG00000127311.10. [Q8NG08-1]
DR Ensembl; ENST00000440906.6; ENSP00000396955.2; ENSG00000127311.10. [Q8NG08-2]
DR Ensembl; ENST00000545134.1; ENSP00000443287.1; ENSG00000127311.10. [Q8NG08-1]
DR GeneID; 92797; -.
DR KEGG; hsa:92797; -.
DR MANE-Select; ENST00000247815.9; ENSP00000247815.5; NM_001370285.1; NP_001357214.1.
DR UCSC; uc001sti.4; human. [Q8NG08-1]
DR CTD; 92797; -.
DR DisGeNET; 92797; -.
DR GeneCards; HELB; -.
DR HGNC; HGNC:17196; HELB.
DR HPA; ENSG00000127311; Low tissue specificity.
DR MIM; 614539; gene.
DR neXtProt; NX_Q8NG08; -.
DR OpenTargets; ENSG00000127311; -.
DR PharmGKB; PA134987279; -.
DR VEuPathDB; HostDB:ENSG00000127311; -.
DR eggNOG; ENOG502QWCN; Eukaryota.
DR GeneTree; ENSGT00390000006913; -.
DR HOGENOM; CLU_510533_0_0_1; -.
DR InParanoid; Q8NG08; -.
DR OMA; CCTKNAY; -.
DR OrthoDB; 174318at2759; -.
DR PhylomeDB; Q8NG08; -.
DR TreeFam; TF336223; -.
DR BRENDA; 3.6.4.12; 2681.
DR PathwayCommons; Q8NG08; -.
DR SignaLink; Q8NG08; -.
DR BioGRID-ORCS; 92797; 11 hits in 1082 CRISPR screens.
DR ChiTaRS; HELB; human.
DR GenomeRNAi; 92797; -.
DR Pharos; Q8NG08; Tbio.
DR PRO; PR:Q8NG08; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8NG08; protein.
DR Bgee; ENSG00000127311; Expressed in bone marrow cell and 111 other tissues.
DR ExpressionAtlas; Q8NG08; baseline and differential.
DR Genevisible; Q8NG08; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0035861; C:site of double-strand break; IMP:UniProtKB.
DR GO; GO:0043139; F:5'-3' DNA helicase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0017116; F:single-stranded DNA helicase activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IMP:UniProtKB.
DR GO; GO:0006269; P:DNA replication, synthesis of RNA primer; IDA:UniProtKB.
DR GO; GO:0000462; P:maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IBA:GO_Central.
DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:1903775; P:regulation of DNA double-strand break processing; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR027044; Helb.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR027785; UvrD-like_helicase_C.
DR PANTHER; PTHR18934:SF135; PTHR18934:SF135; 1.
DR Pfam; PF13538; UvrD_C_2; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Chromosome; Cytoplasm; DNA damage;
KW DNA repair; Helicase; Hydrolase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..1087
FT /note="DNA helicase B"
FT /id="PRO_0000338992"
FT REGION 953..989
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1015..1051
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1055..1078
FT /note="Nuclear export signal"
FT /evidence="ECO:0000269|PubMed:15146062"
FT COMPBIAS 972..986
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1022..1045
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 967
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000269|PubMed:15146062,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 971
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NVF4"
FT MOD_RES 1027
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1048
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NVF4"
FT MOD_RES 1058
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 562..574
FT /note="NYSFYSWTQTMMT -> TLDSYPVLNLVTC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_034086"
FT VAR_SEQ 575..1087
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_034087"
FT VARIANT 172
FT /note="E -> K (in dbSNP:rs35605829)"
FT /id="VAR_043855"
FT VARIANT 191
FT /note="L -> P (in dbSNP:rs4430553)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_043856"
FT VARIANT 267
FT /note="L -> F (in dbSNP:rs35138454)"
FT /id="VAR_043857"
FT VARIANT 575
FT /note="T -> A (in dbSNP:rs58589183)"
FT /id="VAR_061665"
FT VARIANT 966
FT /note="P -> L (in dbSNP:rs1185244)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_043858"
FT VARIANT 980
FT /note="T -> I (in dbSNP:rs1168312)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_043859"
FT MUTAGEN 481
FT /note="K->A: No ATPase activity."
FT /evidence="ECO:0000269|PubMed:12181327,
FT ECO:0000269|PubMed:25617833, ECO:0000269|PubMed:26774285"
FT MUTAGEN 499
FT /note="E->A: Loss of RPA1-binding, leading to impaired
FT recruitment to sites of double-strand breaks; when
FT associated with A-506 and A-510."
FT /evidence="ECO:0000269|PubMed:22194613,
FT ECO:0000269|PubMed:26774285"
FT MUTAGEN 506
FT /note="D->A: Loss of RPA1-binding, leading to impaired
FT recruitment to sites of double-strand breaks; when
FT associated with A-499 and A-510."
FT /evidence="ECO:0000269|PubMed:22194613,
FT ECO:0000269|PubMed:26774285"
FT MUTAGEN 510
FT /note="D->A: Loss of RPA1-binding, leading to impaired
FT recruitment to sites of double-strand breaks; when
FT associated with A-499 and A-506."
FT /evidence="ECO:0000269|PubMed:22194613,
FT ECO:0000269|PubMed:26774285"
FT MUTAGEN 591
FT /note="E->Q: No ATPase activity."
FT /evidence="ECO:0000269|PubMed:12181327,
FT ECO:0000269|PubMed:25617833, ECO:0000269|PubMed:26774285"
FT MUTAGEN 967
FT /note="S->A: Impaired phosphorylation, inducing
FT accumulation in the nucleus."
FT /evidence="ECO:0000269|PubMed:15146062"
FT MUTAGEN 967
FT /note="S->D: Phosphomimetic mutant; leads to higher
FT localization to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:15146062"
FT MUTAGEN 984
FT /note="S->A: Does not affect subcellular location."
FT /evidence="ECO:0000269|PubMed:15146062"
FT MUTAGEN 1005
FT /note="S->A: Does not affect subcellular location."
FT /evidence="ECO:0000269|PubMed:15146062"
FT MUTAGEN 1021
FT /note="S->A: Does not affect subcellular location."
FT /evidence="ECO:0000269|PubMed:15146062"
FT MUTAGEN 1061..1065
FT /note="VSSRL->ASSRA: Accumulation in the nucleus due to
FT defects in nuclear export."
FT /evidence="ECO:0000269|PubMed:15146062"
FT MUTAGEN 1068..1070
FT /note="LRL->ARA: Accumulation in the nucleus due to defects
FT in nuclear export."
FT /evidence="ECO:0000269|PubMed:15146062"
FT CONFLICT 366
FT /note="S -> P (in Ref. 2; BAF83583)"
FT /evidence="ECO:0000305"
FT CONFLICT 849
FT /note="F -> S (in Ref. 2; BAF83583)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1087 AA; 123252 MW; 05220F3186CE722B CRC64;
MARSSPYLRQ LQGPLLPPRD LVEEDDDYLN DDVEEDEESV FIDAEELCSG GVKAGSLPGC
LRVSICDENT QETCKVFGRF PITGAWWRVK VQVKPVVGSR SYQYQVQGFP SYFLQSDMSP
PNQKHICALF LKECEVSSDD VNKFLTWVKE VSNYKNLNFE NLRETLRTFH KETGRKDQKQ
PTQNGQEELF LDNEMSLPLE NTIPFRNVMT ALQFPKIMEF LPVLLPRHFK WIIGSGSKEM
LKEIEEILGT HPWKLGFSKI TYREWKLLRC EASWIAFCQC ESLLQLMTDL EKNALIMYSR
LKQICREDGH TYVEVNDLTL TLSNHMSFHA ASESLKFLKD IGVVTYEKSC VFPYDLYHAE
RAIAFSICDL MKKPPWHLCV DVEKVLASIH TTKPENSSDD ALNESKPDEV RLENPVDVVD
TQDNGDHIWT NGENEINAEI SEVQLDQDQV EVPLDRDQVA ALEMICSNPV TVISGKGGCG
KTTIVSRLFK HIEQLEEREV KKACEDFEQD QNASEEWITF TEQSQLEADK AIEVLLTAPT
GKAAGLLRQK TGLHAYTLCQ VNYSFYSWTQ TMMTTNKPWK FSSVRVLVVD EGSLVSVGIF
KSVLNLLCEH SKLSKLIILG DIRQLPSIEP GNLLKDLFET LKSRNCAIEL KTNHRAESQL
IVDNATRISR RQFPKFDAEL NISDNPTLPI SIQDKTFIFV RLPEEDASSQ SSKTNHHSCL
YSAVKTLLQE NNLQNAKTSQ FIAFRRQDCD LINDCCCKHY TGHLTKDHQS RLVFGIGDKI
CCTRNAYLSD LLPENISGSQ QNNDLDASSE DFSGTLPDFA KNKRDFESNV RLCNGEIFFI
TNDVTDVTFG KRRSLTINNM AGLEVTVDFK KLMKYCRIKH AWARTIHTFQ GSEEQTVVYV
VGKAGRQHWQ HVYTAVTRGR CRVYVIAEES QLRNAIMKNS FPRKTRLKHF LQSKLSSSGA
PPADFPSPRK SSGDSGGPST PSASPLPVVT DHAMTNDVTW SEASSPDERT LTFAERWQLS
SPDGVDTDDD LPKSRASKRT CGVNDDESPS KIFMVGESPQ VSSRLQNLRL NNLIPRQLFK
PTDNQET
