MPH1_SCHPO
ID MPH1_SCHPO Reviewed; 834 AA.
AC Q9UT23;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=ATP-dependent DNA helicase fml1 {ECO:0000305};
DE EC=3.6.4.12 {ECO:0000269|PubMed:22844101};
DE AltName: Full=FANCM-like protein 1 {ECO:0000303|PubMed:18851838};
GN Name=fml1 {ECO:0000303|PubMed:18851838};
GN ORFNames=SPAC9.05 {ECO:0000312|PomBase:SPAC9.05};
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18851838; DOI=10.1016/j.molcel.2008.08.024;
RA Sun W., Nandi S., Osman F., Ahn J.S., Jakovleska J., Lorenz A.,
RA Whitby M.C.;
RT "The FANCM ortholog Fml1 promotes recombination at stalled replication
RT forks and limits crossing over during DNA double-strand break repair.";
RL Mol. Cell 32:118-128(2008).
RN [4]
RP FUNCTION.
RX PubMed=20347428; DOI=10.1016/j.molcel.2010.01.039;
RA Yan Z., Delannoy M., Ling C., Daee D., Osman F., Muniandy P.A., Shen X.,
RA Oostra A.B., Du H., Steltenpool J., Lin T., Schuster B., Decaillet C.,
RA Stasiak A., Stasiak A.Z., Stone S., Hoatlin M.E., Schindler D.,
RA Woodcock C.L., Joenje H., Sen R., de Winter J.P., Li L., Seidman M.M.,
RA Whitby M.C., Myung K., Constantinousend A., Wang W.;
RT "A histone-fold complex and FANCM form a conserved DNA-remodeling complex
RT to maintain genome stability.";
RL Mol. Cell 37:865-878(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-99 AND ASP-196.
RX PubMed=22844101; DOI=10.1093/nar/gks715;
RA Nandi S., Whitby M.C.;
RT "The ATPase activity of Fml1 is essential for its roles in homologous
RT recombination and DNA repair.";
RL Nucleic Acids Res. 40:9584-9595(2012).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF LYS-99 AND ASP-196.
RX PubMed=22723423; DOI=10.1126/science.1220111;
RA Lorenz A., Osman F., Sun W., Nandi S., Steinacher R., Whitby M.C.;
RT "The fission yeast FANCM ortholog directs non-crossover recombination
RT during meiosis.";
RL Science 336:1585-1588(2012).
RN [7]
RP RETRACTED PAPER.
RX PubMed=24026537; DOI=10.1098/rsob.130102;
RA Bhattacharjee S., Osman F., Feeney L., Lorenz A., Bryer C., Whitby M.C.;
RT "MHF1-2/CENP-S-X performs distinct roles in centromere metabolism and
RT genetic recombination.";
RL Open Biol. 3:130102-130102(2013).
RN [8]
RP RETRACTION NOTICE OF PUBMED:24026537.
RX PubMed=29445032; DOI=10.1098/rsob.180010;
RA Bhattacharjee S., Osman F., Feeney L., Lorenz A., Bryer C., Whitby M.C.;
RL Open Biol. 8:180010-180010(2018).
CC -!- FUNCTION: ATP-dependent DNA helicase involved in DNA damage repair by
CC homologous recombination and in genome maintenance. Capable of
CC unwinding D-loops (PubMed:18851838, PubMed:22844101, PubMed:22723423).
CC Plays a role in limiting crossover recombinantion during mitotic DNA
CC double-strand break (DSB) repair (PubMed:18851838). Component of a
CC FANCM-MHF complex which promotes gene conversion at blocked replication
CC forks, probably by reversal of the stalled fork (PubMed:18851838,
CC PubMed:20347428). FANCM-MHF also promotes non-crossover recombination
CC in meiotic cells (PubMed:22723423). {ECO:0000269|PubMed:18851838,
CC ECO:0000269|PubMed:20347428, ECO:0000269|PubMed:22723423,
CC ECO:0000269|PubMed:22844101}.
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:22844101};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:16823372}.
CC -!- DISRUPTION PHENOTYPE: Hypersensitive to the alkylating agent methyl
CC methanesulfonate (MMS) and the cross-linking agent cisplatin.
CC {ECO:0000269|PubMed:18851838}.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DEAH subfamily.
CC FANCM sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: Several phenotypes were reported for a triple-alanine mutant.
CC However this data was retracted as several constructs contained a C-
CC terminal deletion instead of the reported triple-alanine mutation.
CC Following strain regeneration, although many phenotypes were not
CC reproducible, the central observations of the publication were
CC confirmed. {ECO:0000305|PubMed:24026537, ECO:0000305|PubMed:29445032}.
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DR EMBL; CU329670; CAB57423.2; -; Genomic_DNA.
DR PIR; T39190; T39190.
DR RefSeq; NP_593348.2; NM_001018780.3.
DR AlphaFoldDB; Q9UT23; -.
DR SMR; Q9UT23; -.
DR BioGRID; 280082; 53.
DR STRING; 4896.SPAC9.05.1; -.
DR iPTMnet; Q9UT23; -.
DR SwissPalm; Q9UT23; -.
DR MaxQB; Q9UT23; -.
DR PaxDb; Q9UT23; -.
DR EnsemblFungi; SPAC9.05.1; SPAC9.05.1:pep; SPAC9.05.
DR GeneID; 2543668; -.
DR KEGG; spo:SPAC9.05; -.
DR PomBase; SPAC9.05; fml1.
DR VEuPathDB; FungiDB:SPAC9.05; -.
DR eggNOG; KOG0354; Eukaryota.
DR HOGENOM; CLU_002513_0_2_1; -.
DR InParanoid; Q9UT23; -.
DR OMA; HRAVGNY; -.
DR PhylomeDB; Q9UT23; -.
DR PRO; PR:Q9UT23; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0071821; C:FANCM-MHF complex; ISS:PomBase.
DR GO; GO:0005730; C:nucleolus; HDA:PomBase.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
DR GO; GO:0035861; C:site of double-strand break; IDA:PomBase.
DR GO; GO:0043138; F:3'-5' DNA helicase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0000400; F:four-way junction DNA binding; IDA:PomBase.
DR GO; GO:0009378; F:four-way junction helicase activity; IDA:PomBase.
DR GO; GO:0045003; P:double-strand break repair via synthesis-dependent strand annealing; IMP:PomBase.
DR GO; GO:0036297; P:interstrand cross-link repair; IMP:PomBase.
DR GO; GO:1902346; P:meiotic strand displacement involved in double-strand break repair via SDSA; IDA:PomBase.
DR GO; GO:1903461; P:Okazaki fragment processing involved in mitotic DNA replication; ISO:PomBase.
DR GO; GO:0007131; P:reciprocal meiotic recombination; IMP:PomBase.
DR GO; GO:0031297; P:replication fork processing; IMP:PomBase.
DR GO; GO:0071932; P:replication fork reversal; IDA:PomBase.
DR GO; GO:0000732; P:strand displacement; IDA:PomBase.
DR CDD; cd18033; DEXDc_FANCM; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR002464; DNA/RNA_helicase_DEAH_CS.
DR InterPro; IPR039686; FANCM/Mph1-like.
DR InterPro; IPR044749; FANCM_DEXDc.
DR InterPro; IPR006935; Helicase/UvrB_N.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR14025:SF20; PTHR14025:SF20; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF04851; ResIII; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00690; DEAH_ATP_HELICASE; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; DNA damage; DNA repair; DNA-binding; Helicase;
KW Hydrolase; Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..834
FT /note="ATP-dependent DNA helicase fml1"
FT /id="PRO_0000310751"
FT DOMAIN 80..248
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 416..582
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 650..690
FT /note="Interaction with MHF complex"
FT /evidence="ECO:0000269|PubMed:24026537"
FT REGION 738..769
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 196..199
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 93..100
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MUTAGEN 99
FT /note="K->R: Retains DNA-binding activity but is unable to
FT unwind D loops or dissociate synthetic HJs."
FT /evidence="ECO:0000269|PubMed:22723423,
FT ECO:0000269|PubMed:22844101"
FT MUTAGEN 196
FT /note="D->N: Retains DNA-binding activity but is unable to
FT unwind D loops or dissociate synthetic HJs."
FT /evidence="ECO:0000269|PubMed:22723423,
FT ECO:0000269|PubMed:22844101"
SQ SEQUENCE 834 AA; 96555 MW; 987AD715109C8215 CRC64;
MSDDSFSSDE DWDELDTQVV DKIENEYHNN TIGLNGYSVD EYFDANDSNR YRLQHELDES
AAQQWVYPIN VSFRDYQFNI VQKALFENVL VALPTGLGKT FIAAVVMMNY LRWFPKSYIV
FMAPTKPLVT QQMEACYKIT GIPKSQTAEL SGHVPVTTRN QYYQSRNVFF VTPQTILNDI
KHGICDRTRI SCLVIDEAHR STGNYAYVEV VHLLSLSNKN FRILALSATP GNKLEAIQNV
IDSLHISRIE IRTENSIDIS QYVQKKEVDF FPVDLSAEIT DIRDRFSSIL EPMLQKLNKG
NYYRIQNAKD ITSFTVVQAK QAFLAMSGQN FPANQKWDIL NTFDALATFA YPLNLLLNHG
IRPFYQKLRE VEEECFVGRS GYKKRIINHE NYRPLMDDIE ILLRDQSFVG HPKLEHLERI
VTEYFEKEQT KDTRIMIFVE IRSSAEEILR FLGKFYPNVR PAIFIGQSAV RKAAGMSQKL
QNETVKQFQK GEVNTLIATS IGEEGLDIGE VDMIICYDAS ASPIRMLQRM GRTGRKRKGY
IYMLLTRGKE EAKWERAKDA YRTLQDNIVS GRGLSLSEKS YRILPEKFRP VCDKRVIEIP
KENEEVVVAP KKVQLRTKIK KKFFMPENAL NGFITASALG KPKRALAKSE ESPFEICPVT
YSIEQEKKLE KYKRVCLRGL DIHRNRRLSQ LSVTGRIPHS LATKSIHSFL KHLNTIDSQK
AQEWRREINN QFQVSNINST DRDTKQPKMH DFRQPLHPNP MTTLKRKGQH NSFSYDKSTL
FYDNNNNLEE DLPDVNISIS SRNEEASKTK PFDDRQQRLQ QLVEKRKRMK GMLI
