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   27-MAR-2024, entry version 140.
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   PDB; 7XV1; X-ray; 1.80 A; B=496-519.
DR   PDBsum; 7XV1; -.
DR   AlphaFoldDB; Q8NG08; -.
DR   SMR; Q8NG08; -.
DR   BioGRID; 124978; 20.
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; 9606-ENSP00000247815; -.
DR   PeptideAtlas; Q8NG08; -.
DR   ProteomicsDB; 73405; -. [Q8NG08-1]
DR   ProteomicsDB; 73406; -. [Q8NG08-2]
DR   Pumba; Q8NG08; -.
DR   Antibodypedia; 16658; 38 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   AGR; HGNC:17196; -.
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; CTKNAYL; -.
DR   OrthoDB; 5305157at2759; -.
DR   PhylomeDB; Q8NG08; -.
DR   TreeFam; TF336223; -.
DR   BRENDA; 3.6.4.12; 2681.
DR   PathwayCommons; Q8NG08; -.
DR   SignaLink; Q8NG08; -.
DR   BioGRID-ORCS; 92797; 14 hits in 1162 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 male germ line stem cell (sensu Vertebrata) in testis and 112 other cell types or tissues.
DR   ExpressionAtlas; Q8NG08; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0016604; C:nuclear body; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
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:0017116; F:single-stranded DNA helicase activity; IDA:UniProtKB.
DR   GO; GO:0006974; P:DNA damage response; 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: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   CDD; cd17933; DEXSc_RecD-like; 1.
DR   CDD; cd18809; SF1_C_RecD; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR027785; UvrD-like_helicase_C.
DR   PANTHER; PTHR43788:SF21; DNA HELICASE B; 1.
DR   PANTHER; PTHR43788; DNA2/NAM7 HELICASE FAMILY MEMBER; 1.
DR   Pfam; PF13604; AAA_30; 1.
DR   Pfam; PF13538; UvrD_C_2; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2.
DR   Genevisible; Q8NG08; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Chromosome; Cytoplasm;
KW   DNA damage; 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"
FT   HELIX           496..508
FT                   /evidence="ECO:0007829|PDB:7XV1"
FT   HELIX           515..517
FT                   /evidence="ECO:0007829|PDB:7XV1"
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
//