MPH1_YEAST
ID MPH1_YEAST Reviewed; 993 AA.
AC P40562; D6VVT2;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=ATP-dependent DNA helicase MPH1 {ECO:0000305};
DE EC=3.6.4.12 {ECO:0000269|PubMed:15634678};
DE AltName: Full=FANCM-like protein 1 {ECO:0000250|UniProtKB:Q9UT23};
DE AltName: Full=Mutator phenotype protein 1 {ECO:0000303|PubMed:10628851};
GN Name=MPH1 {ECO:0000303|PubMed:10628851};
GN OrderedLocusNames=YIR002C {ECO:0000312|SGD:S000001441}; ORFNames=YIB2C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7762303; DOI=10.1002/yea.320110109;
RA Voss H., Tamames J., Teodoru C., Valencia A., Sensen C., Wiemann S.,
RA Schwager C., Zimmermann J., Sander C., Ansorge W.;
RT "Nucleotide sequence and analysis of the centromeric region of yeast
RT chromosome IX.";
RL Yeast 11:61-78(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169870;
RA Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D.,
RA Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E.,
RA Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C.,
RA Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V.,
RA Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.";
RL Nature 387:84-87(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP GENE NAME.
RX PubMed=10628851; DOI=10.1007/pl00013817;
RA Entian K.-D., Schuster T., Hegemann J.H., Becher D., Feldmann H.,
RA Gueldener U., Goetz R., Hansen M., Hollenberg C.P., Jansen G., Kramer W.,
RA Klein S., Koetter P., Kricke J., Launhardt H., Mannhaupt G., Maierl A.,
RA Meyer P., Mewes W., Munder T., Niedenthal R.K., Ramezani Rad M.,
RA Roehmer A., Roemer A., Rose M., Schaefer B., Siegler M.-L., Vetter J.,
RA Wilhelm N., Wolf K., Zimmermann F.K., Zollner A., Hinnen A.;
RT "Functional analysis of 150 deletion mutants in Saccharomyces cerevisiae by
RT a systematic approach.";
RL Mol. Gen. Genet. 262:683-702(1999).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10880470; DOI=10.1093/genetics/155.3.1069;
RA Scheller J., Schuerer K.A., Rudolph C., Hettwer S., Kramer W.;
RT "MPH1, a yeast gene encoding a DEAH protein, plays a role in protection of
RT the genome from spontaneous and chemically induced damage.";
RL Genetics 155:1069-1081(2000).
RN [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [7]
RP FUNCTION.
RX PubMed=15126389; DOI=10.1534/genetics.166.4.1673;
RA Schuerer K.A., Rudolph C., Ulrich H.D., Kramer W.;
RT "Yeast MPH1 gene functions in an error-free DNA damage bypass pathway that
RT requires genes from homologous recombination, but not from postreplicative
RT repair.";
RL Genetics 166:1673-1686(2004).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15634678; DOI=10.1074/jbc.m413898200;
RA Prakash R., Krejci L., Van Komen S., Schuerer K.A., Kramer W., Sung P.;
RT "Saccharomyces cerevisiae MPH1 gene, required for homologous recombination-
RT mediated mutation avoidance, encodes a 3' to 5' DNA helicase.";
RL J. Biol. Chem. 280:7854-7860(2005).
RN [9]
RP FUNCTION.
RX PubMed=16121259; DOI=10.1371/journal.pgen.0010024;
RA Lee W., St Onge R.P., Proctor M., Flaherty P., Jordan M.I., Arkin A.P.,
RA Davis R.W., Nislow C., Giaever G.;
RT "Genome-wide requirements for resistance to functionally distinct DNA-
RT damaging agents.";
RL PLoS Genet. 1:235-246(2005).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19136626; DOI=10.1101/gad.1737809;
RA Prakash R., Satory D., Dray E., Papusha A., Scheller J., Kramer W.,
RA Krejci L., Klein H., Haber J.E., Sung P., Ira G.;
RT "Yeast Mph1 helicase dissociates Rad51-made D-loops: implications for
RT crossover control in mitotic recombination.";
RL Genes Dev. 23:67-79(2009).
RN [12]
RP FUNCTION.
RX PubMed=19181670; DOI=10.1074/jbc.m808894200;
RA Kang Y.H., Kang M.J., Kim J.H., Lee C.H., Cho I.T., Hurwitz J., Seo Y.S.;
RT "The MPH1 gene of Saccharomyces cerevisiae functions in Okazaki fragment
RT processing.";
RL J. Biol. Chem. 284:10376-10386(2009).
RN [13]
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 [14]
RP FUNCTION.
RX PubMed=22912599; DOI=10.1371/journal.pgen.1002884;
RA Ward T.A., Dudasova Z., Sarkar S., Bhide M.R., Vlasakova D., Chovanec M.,
RA McHugh P.J.;
RT "Components of a Fanconi-like pathway control Pso2-independent DNA
RT interstrand crosslink repair in yeast.";
RL PLoS Genet. 8:e1002884-e1002884(2012).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24119400; DOI=10.1016/j.molcel.2013.09.007;
RA Mazon G., Symington L.S.;
RT "Mph1 and Mus81-Mms4 prevent aberrant processing of mitotic recombination
RT intermediates.";
RL Mol. Cell 52:63-74(2013).
RN [16]
RP FUNCTION, INTERACTION WITH FKH1, DOMAIN, DISRUPTION PHENOTYPE, MUTAGENESIS
RP OF ASP-774; SER-775; THR-776; GLU-777; SER-782; GLU-784; THR-785 AND
RP GLU-786, AND PHOSPHORYLATION AT THR-776 AND THR-785.
RX PubMed=27257873; DOI=10.1371/journal.pgen.1006094;
RA Dummer A.M., Su Z., Cherney R., Choi K., Denu J., Zhao X., Fox C.A.;
RT "Binding of the Fkh1 forkhead associated domain to a phosphopeptide within
RT the Mph1 DNA helicase regulates mating-type switching in budding yeast.";
RL PLoS Genet. 12:e1006094-e1006094(2016).
CC -!- FUNCTION: ATP-dependent DNA helicase involved in DNA damage repair by
CC homologous recombination and in genome maintenance (PubMed:10880470,
CC PubMed:15126389, PubMed:15634678, PubMed:16121259). Capable of
CC unwinding D-loops (PubMed:19136626). Plays a role in limiting crossover
CC recombinants during mitotic DNA double-strand break (DSB) repair
CC (PubMed:19136626). Prevents crossovers between ectopic sequences by
CC removing substrates for MUS81-MMS4 or RAD1-RAD10 cleavage
CC (PubMed:24119400). Component of a FANCM-MHF complex which promotes gene
CC conversion at blocked replication forks, probably by reversal of the
CC stalled fork (Probable) (PubMed:22912599). Binds to flap-structured DNA
CC but not to non-flap nicked DNA, and participates in Okazaki fragment
CC processing by stimulating the endonuclease activities of FEN1 and DNA2
CC (PubMed:19181670). Involved in recombination donor preference during
CC mating-type switching via interaction with FKH1 (PubMed:27257873).
CC {ECO:0000269|PubMed:10880470, ECO:0000269|PubMed:15126389,
CC ECO:0000269|PubMed:15634678, ECO:0000269|PubMed:16121259,
CC ECO:0000269|PubMed:19136626, ECO:0000269|PubMed:19181670,
CC ECO:0000269|PubMed:22912599, ECO:0000269|PubMed:24119400,
CC ECO:0000269|PubMed:27257873, ECO:0000305|PubMed:20347428}.
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:15634678};
CC -!- SUBUNIT: Interacts with the MHF histone-fold complex composed of MHF1
CC and MHF2 to form the FANCM-MHF complex (By similarity). Interacts with
CC FHK1 (PubMed:27257873). {ECO:0000250|UniProtKB:Q9UT23,
CC ECO:0000269|PubMed:27257873}.
CC -!- INTERACTION:
CC P40562; Q08204: SMC5; NbExp=5; IntAct=EBI-25369, EBI-34125;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10880470,
CC ECO:0000269|PubMed:14562095}.
CC -!- PTM: Phosphorylation at both Thr-776 and Thr-785 is required for the
CC interaction with FKH1. {ECO:0000269|PubMed:27257873}.
CC -!- DISRUPTION PHENOTYPE: Causes transiant accumulation of ectopic joint
CC molecules (JMs) (PubMed:24119400). Leads to a defect in donor
CC preference during mating-type switching (PubMed:27257873). Does not
CC affect FKH1's overlapping role with FKH2 of regulation of the
CC expression of the CLB2 cluster of genes during the G2/M phase of the
CC mitotic cell cycle (PubMed:27257873). {ECO:0000269|PubMed:24119400,
CC ECO:0000269|PubMed:27257873, ECO:0000303|PubMed:27257873}.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DEAH subfamily.
CC FANCM sub-subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X79743; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z38062; CAA86204.1; -; Genomic_DNA.
DR EMBL; BK006942; DAA08548.1; -; Genomic_DNA.
DR PIR; S48436; S48436.
DR RefSeq; NP_012267.1; NM_001179524.1.
DR AlphaFoldDB; P40562; -.
DR SMR; P40562; -.
DR BioGRID; 34993; 334.
DR DIP; DIP-5016N; -.
DR IntAct; P40562; 9.
DR STRING; 4932.YIR002C; -.
DR iPTMnet; P40562; -.
DR MaxQB; P40562; -.
DR PaxDb; P40562; -.
DR PRIDE; P40562; -.
DR EnsemblFungi; YIR002C_mRNA; YIR002C; YIR002C.
DR GeneID; 854818; -.
DR KEGG; sce:YIR002C; -.
DR SGD; S000001441; MPH1.
DR VEuPathDB; FungiDB:YIR002C; -.
DR eggNOG; KOG0354; Eukaryota.
DR GeneTree; ENSGT00940000156480; -.
DR HOGENOM; CLU_002513_1_0_1; -.
DR InParanoid; P40562; -.
DR OMA; IRPHIFI; -.
DR BioCyc; YEAST:G3O-31423-MON; -.
DR BRENDA; 3.6.4.12; 984.
DR PRO; PR:P40562; -.
DR Proteomes; UP000002311; Chromosome IX.
DR RNAct; P40562; protein.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0043138; F:3'-5' DNA helicase activity; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0033677; F:DNA/RNA helicase activity; IDA:SGD.
DR GO; GO:0070336; F:flap-structured DNA binding; IDA:SGD.
DR GO; GO:0000400; F:four-way junction DNA binding; IBA:GO_Central.
DR GO; GO:0009378; F:four-way junction helicase activity; IBA:GO_Central.
DR GO; GO:0033567; P:DNA replication, Okazaki fragment processing; IGI:SGD.
DR GO; GO:0007535; P:donor selection; IMP:SGD.
DR GO; GO:0045003; P:double-strand break repair via synthesis-dependent strand annealing; IBA:GO_Central.
DR GO; GO:0036297; P:interstrand cross-link repair; IGI:SGD.
DR GO; GO:0060543; P:negative regulation of strand invasion; IDA:SGD.
DR GO; GO:0000725; P:recombinational repair; IMP:SGD.
DR GO; GO:0071932; P:replication fork reversal; IBA:GO_Central.
DR CDD; cd18033; DEXDc_FANCM; 1.
DR Gene3D; 3.40.50.300; -; 2.
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; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 1: Evidence at protein level;
KW ATP-binding; DNA damage; DNA repair; DNA-binding; Helicase; Hydrolase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..993
FT /note="ATP-dependent DNA helicase MPH1"
FT /id="PRO_0000055193"
FT DOMAIN 94..261
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 507..655
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 530..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 751..810
FT /note="FKH1-binding region"
FT /evidence="ECO:0000269|PubMed:27257873"
FT MOTIF 209..212
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 107..114
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOD_RES 776
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:27257873"
FT MOD_RES 785
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:27257873"
FT MUTAGEN 774
FT /note="D->A: Reduces the interaction with FKH1; when
FT associated with A-785."
FT /evidence="ECO:0000269|PubMed:27257873"
FT MUTAGEN 775
FT /note="S->A: Reduces the interaction with FKH1; when
FT associated with A-785."
FT /evidence="ECO:0000269|PubMed:27257873"
FT MUTAGEN 776
FT /note="T->A: Abolishes the interaction with FKH1; when
FT associated with A-785."
FT /evidence="ECO:0000269|PubMed:27257873"
FT MUTAGEN 777
FT /note="E->A: Reduces the interaction with FKH1; when
FT associated with A-785."
FT /evidence="ECO:0000269|PubMed:27257873"
FT MUTAGEN 782
FT /note="S->A: Reduces the interaction with FKH1; when
FT associated with A-776."
FT /evidence="ECO:0000269|PubMed:27257873"
FT MUTAGEN 784
FT /note="E->A: Reduces the interaction with FKH1; when
FT associated with A-776."
FT /evidence="ECO:0000269|PubMed:27257873"
FT MUTAGEN 785
FT /note="T->A: Abolishes the interaction with FKH1; when
FT associated with A-776."
FT /evidence="ECO:0000269|PubMed:27257873"
FT MUTAGEN 786
FT /note="E->A: Reduces the interaction with FKH1; when
FT associated with A-776."
FT /evidence="ECO:0000269|PubMed:27257873"
SQ SEQUENCE 993 AA; 114058 MW; 474DDC99C543171F CRC64;
MASADDYFSD FEDDELDKLY EKAINKSVKE TITRRAVPVQ KDLHDNVLPG QKTVYEEIQR
DVSFGPTHHE LDYDALSFYV YPTNYEVRDY QYTIVHKSLF QNTLCAIPTG MGKTFIASTV
MLNYFRWTKK AKIIFTAPTR PLVAQQIKAC LGITGIPSDQ TAILLDKSRK NREEIWANKR
VFFATPQVVE NDLKRGVLDP KDIVCLVIDE AHRATGSSAY TNVVKFIDRF NSSYRLLALT
ATPASDLEGV QEVVNNLDIS KIEIRTEESM DIVKYMKKRK KEKIEVPLLL EIEDIIEQLG
MAVKPVLQQA IELGIYEECD PSQINAFKAM QQSQKIIANP TIPEGIKWRN FFILQLLNNV
GQMLKRLKIY GIRTFFNYFQ NKCTEFTTKY NLKKSTNKIA AEFYYHPILK NIKNQCENYL
SDPKFVGHGK LQCVRDELMD FFQKRGSDSR VIIFTELRES ALEIVKFIDS VADDQIRPHI
FIGQARAKEG FDEVKYTRKH APKGRKKVER LHRQEQEKFL EAERTKRAAN DKLERSARRT
GSSEEAQISG MNQKMQKEVI HNFKKGEYNV LVCTSIGEEG LDIGEVDLII CYDTTSSPIK
NIQRMGRTGR KRDGKIVLLF SSNESYKFER AMEDYSTLQA LISKQCIDYK KSDRIIPEDI
IPECHETLIT INDENEIINE MEDVDEVIRY ATQCMMGKKV KPKKAITKKK RVQENKKPKK
FFMPDNVETS IVSASTLINK FLVNESGGKQ LVTSNENPSK KRKIFKALDN LENDSTEEAS
SSLETEDEEV SDDNNVFIAE GQNGCQKDLE TAIIRTGESL TTLKPLHNFE RPNMALFVND
CGLPTKIEKN VKDIRGNQHN LEKEKSCTVD KNNMVLSLDD WNFFRNRYIP EGVSFDVEPN
FVQYTKGVKV PHCHKVSKII TLFNDESNDN KKRTIDMNYT KCLARGMLRD EKKFVKVNDK
SQVDNNSVNH DSSQSFTLSN AELDDILGSD SDF
