HELB_MOUSE
ID HELB_MOUSE Reviewed; 1074 AA.
AC Q6NVF4; G5E835; Q6KAT5; Q8C930; Q9EQT8;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=DNA helicase B {ECO:0000305};
DE EC=3.6.4.12 {ECO:0000250|UniProtKB:Q8NG08};
GN Name=Helb {ECO:0000312|MGI:MGI:2152895};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 69-82; 632-648 AND 797-814,
RP AND FUNCTION.
RC TISSUE=Fetal brain;
RX PubMed=11557815; DOI=10.1093/nar/29.18.3835;
RA Tada S., Kobayashi T., Omori A., Kusa Y., Okumura N., Kodaira H.,
RA Ishimi Y., Seki M., Enomoto T.;
RT "Molecular cloning of a cDNA encoding mouse DNA helicase B, which has
RT homology to Escherichia coli RecD protein, and identification of a mutation
RT in the DNA helicase B from tsFT848 temperature-sensitive DNA replication
RT mutant cells.";
RL Nucleic Acids Res. 29:3835-3840(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryonic tail;
RX PubMed=15449545; DOI=10.1093/dnares/11.2.127;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of FLJ genes: the
RT complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified
RT by screening of terminal sequences of cDNA clones randomly sampled from
RT size-fractionated libraries.";
RL DNA Res. 11:127-135(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-168.
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [7]
RP FUNCTION.
RX PubMed=7794903; DOI=10.1021/bi00024a016;
RA Matsumoto K., Seki M., Masutani C., Tada S., Enomoto T., Ishimi Y.;
RT "Stimulation of DNA synthesis by mouse DNA helicase B in a DNA replication
RT system containing eukaryotic replication origins.";
RL Biochemistry 34:7913-7922(1995).
RN [8]
RP FUNCTION.
RX PubMed=7596831; DOI=10.1093/nar/23.11.2014;
RA Saitoh A., Tada S., Katada T., Enomoto T.;
RT "Stimulation of mouse DNA primase-catalyzed oligoribonucleotide synthesis
RT by mouse DNA helicase B.";
RL Nucleic Acids Res. 23:2014-2018(1995).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-942 AND SER-946, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-942; SER-946; THR-992 AND
RP SER-1015, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-462 AND
RP 1029-VAL--LEU-1038.
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:26774285). Recruitment to
CC single-stranded DNA (ssDNA) following DNA damage leads to inhibit the
CC nucleases catalyzing resection, such as EXO1, BLM and DNA2, possibly
CC via the 5'-3' ssDNA translocase activity of HELB (PubMed:26774285). As
CC cells approach S phase, DNA end resection is promoted by the nuclear
CC export of HELB following phosphorylation (PubMed:26774285). Acts
CC independently of TP53BP1 (PubMed:26774285). Unwinds duplex DNA with 5'-
CC 3' polarity. Has single-strand DNA-dependent ATPase and DNA helicase
CC activities. Prefers ATP and dATP as substrates. During S phase, may
CC facilitate cellular recovery from replication stress (PubMed:11557815,
CC PubMed:7596831, PubMed:7794903). {ECO:0000269|PubMed:11557815,
CC ECO:0000269|PubMed:26774285, ECO:0000269|PubMed:7596831,
CC ECO:0000269|PubMed:7794903}.
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:Q8NG08};
CC -!- SUBUNIT: Binds to RPA1; this interaction promotes HELB recruitment to
CC chromatin following DNA damage. Interacts with at least two subunits of
CC the DNA polymerase alpha complex. Interacts with CDC45. Interacts with
CC TOPB1. {ECO:0000250|UniProtKB:Q8NG08}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26774285}. Cytoplasm
CC {ECO:0000269|PubMed:26774285}. Chromosome
CC {ECO:0000250|UniProtKB:Q8NG08}. Note=Predominantly nuclear.
CC Phosphorylation at Ser-942 by CDK2 during the G1/S transition results
CC in its nuclear export into the cytoplasm as cells approach and progress
CC through S phase. Following DNA damage, recruited to sites of double-
CC strand breaks by the RPA complex. {ECO:0000250|UniProtKB:Q8NG08}.
CC -!- PTM: Phosphorylated at Ser-942 by CDK2 during the G1/S transition,
CC resulting in its nuclear export into the cytoplasm. As S phase
CC progresses, its exclusion from the nucleus promotes the activation of
CC long-range resection. {ECO:0000250|UniProtKB:Q8NG08}.
CC -!- SIMILARITY: Belongs to the RecD family. HELB subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD21372.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB048542; BAB20809.1; -; mRNA.
DR EMBL; AK131122; BAD21372.1; ALT_INIT; mRNA.
DR EMBL; AC134326; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC144942; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466578; EDL24397.1; -; Genomic_DNA.
DR EMBL; BC068140; AAH68140.1; -; mRNA.
DR EMBL; AK043127; BAC31468.1; -; mRNA.
DR CCDS; CCDS24203.1; -.
DR RefSeq; NP_536694.2; NM_080446.2.
DR AlphaFoldDB; Q6NVF4; -.
DR BioGRID; 228238; 6.
DR STRING; 10090.ENSMUSP00000020449; -.
DR iPTMnet; Q6NVF4; -.
DR PhosphoSitePlus; Q6NVF4; -.
DR EPD; Q6NVF4; -.
DR jPOST; Q6NVF4; -.
DR MaxQB; Q6NVF4; -.
DR PaxDb; Q6NVF4; -.
DR PeptideAtlas; Q6NVF4; -.
DR PRIDE; Q6NVF4; -.
DR ProteomicsDB; 269730; -.
DR Antibodypedia; 16658; 33 antibodies from 17 providers.
DR DNASU; 117599; -.
DR Ensembl; ENSMUST00000020449; ENSMUSP00000020449; ENSMUSG00000020228.
DR GeneID; 117599; -.
DR KEGG; mmu:117599; -.
DR UCSC; uc007hes.2; mouse.
DR CTD; 92797; -.
DR MGI; MGI:2152895; Helb.
DR VEuPathDB; HostDB:ENSMUSG00000020228; -.
DR eggNOG; ENOG502QWCN; Eukaryota.
DR GeneTree; ENSGT00390000006913; -.
DR HOGENOM; CLU_010264_0_0_1; -.
DR InParanoid; Q6NVF4; -.
DR OMA; CCTKNAY; -.
DR OrthoDB; 174318at2759; -.
DR PhylomeDB; Q6NVF4; -.
DR TreeFam; TF336223; -.
DR BioGRID-ORCS; 117599; 1 hit in 106 CRISPR screens.
DR ChiTaRS; Helb; mouse.
DR PRO; PR:Q6NVF4; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q6NVF4; protein.
DR Bgee; ENSMUSG00000020228; Expressed in ileal epithelium and 234 other tissues.
DR ExpressionAtlas; Q6NVF4; baseline and differential.
DR Genevisible; Q6NVF4; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005662; C:DNA replication factor A complex; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0043139; F:5'-3' DNA helicase activity; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003678; F:DNA helicase activity; IDA:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0017116; F:single-stranded DNA helicase activity; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0006260; P:DNA replication; ISO:MGI.
DR GO; GO:0006269; P:DNA replication, synthesis of RNA primer; ISO:MGI.
DR GO; GO:0006261; P:DNA-templated DNA replication; IDA:MGI.
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 ATP-binding; Chromosome; Cytoplasm; Direct protein sequencing; Helicase;
KW Hydrolase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..1074
FT /note="DNA helicase B"
FT /id="PRO_0000338993"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 380..420
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 932..1014
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1040..1074
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1022..1046
FT /note="Nuclear export signal"
FT /evidence="ECO:0000269|PubMed:26774285"
FT COMPBIAS 1..22
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 23..38
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 932..950
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 971..1014
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1040..1064
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 942
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 946
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 992
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1015
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1026
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NG08"
FT MUTAGEN 462
FT /note="K->A: No ATPase activity."
FT /evidence="ECO:0000269|PubMed:26774285"
FT MUTAGEN 1029..1038
FT /note="VSSVFQNMRL->ASSVAQNARA: Accumulation in the nucleus
FT due to defects in nuclear export."
FT /evidence="ECO:0000269|PubMed:26774285"
FT CONFLICT 805
FT /note="T -> I (in Ref. 5; AAH68140)"
FT /evidence="ECO:0000305"
FT CONFLICT 933
FT /note="S -> T (in Ref. 1; BAB20809)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1074 AA; 121471 MW; 0D17C06D429BADC8 CRC64;
MARQDRLREL LGPLHPYKSD DEEEDCAQEE EGEQEEEFVD AEELCSGGIK AGSLPGRARV
SIPDEYTKEK CTVYGRFPLK GPWWRVKVQV LKPQRSRSYQ VQGFPAYFLQ VDMSPPDQKQ
ICSLFLKECN LASERIQEFL KWVEKVSSFE NLHFENLWET LRLFYRETEK KDKKLSTPRE
QQGEEMRVEK SFAFISAMVA LQFPKVMEFL PSLFPRHFKR LISSSSDWVL GCIEDVLGTQ
PWKLGFRRIT YREMKLVRCE ASWTAFSQCP SLLQLMTPLQ KNALVIYSKL RQTCREDGHT
YIEVKDLTSG LSEHMSFEEA CQSLAFLKDI DVVIYEKDYV FLSELYEAEQ DIASSICELM
SRPPWHLKVD VKNVLASIRG AKPNDPGSAE AVEGSKPEEV GSEQGDSVLD AQDGDDHVRS
NGEHVANAEI NDVPLDQDQV VALETICANA VTVLSGKGGC GKTTIVSRLF KHMEHLEETE
VQQACEDFEQ DQEASEEWLD CPKQSPAGVD KAVEVLLTAP TGKAAGLLRQ RTDLPAYTLC
QVNYSFYMWK TKNEVDKPWK FSTVRVLVVD EGSLVSVGIF KSVLQLLCKH SKLSKLIILG
DVRQLPSIEP GNMLQDVFET LKSRQCAIEL KTNHRTESQL IVDNATRISR RQFPKFDAEL
NICGNPTLPL SIQDKTFIFV RLPEEDSRSQ SSKGEHRSNL YTAVKTLLQG KDFCSFESSK
TSQFIAFRRQ DCDLINDCCC KHYTGHLIKD HEKKLIFAVG DKICCTRNAY LSDLLPDKDQ
EAEGKGYGDA PDDDAKIKQD FESSTRLCNG EIFFITRDVT DVTFKRKRLL TINNEAGLEV
TVDFSKLMAN CQIKHAWART IHTFQGSEEN TVVYVVGKAG RQHWQHVYTA VTRGRSRVYI
IAQESELRSA TRKRGFPRQT RLKHFLQKKL SGSCAPSTGF ASQPSSPRVG GRPDTQPPAS
HLCRTPDNKA TADSARGDER WLSASVNDDV DTDEESAQLR GSKRIGDGFP FDEESPSKFR
MVEAPSPQVS SVFQNMRLNT LTPRQLFKPT DNQDTGTAGV ADDANDPSNQ EMEM
