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Protein

Crossover junction endonuclease MMS4

Gene

MMS4

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Interacts with MUS81 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, D-loops, replication forks with regressed leading strands and nicked Holliday junctions. Cleavage probably occurs approximately half a helical turn upstream of the free 5'-end in these structures. May be required in mitosis for the processing of stalled replication fork intermediates arising spontaneously or subsequent to treatment with DNA damaging agents such as methylmethane sulfonate (MMS), camptothecin (CPT) or UV. May be required in meiosis for the repair of meiosis-specific double strand breaks subsequent to single-end invasion (SEI). This involves consecutive cleavage of D-loops and nicked Holliday junctions leading to sister chromatid crossover. In contrast to MSH4-MSH5 dependent crossover, double Holliday junctions do not seem to be involved. Spore formation and viability are severely impaired in deletion strains.11 Publications

Cofactori

Mg2+1 Publication, Mn2+1 Publication

Kineticsi

  1. KM=31.1 nM for a nicked Holliday junction1 Publication
  2. KM=6.84 nM for a regressed leading strand replication fork1 Publication
  3. KM=4.8 nM for for a 3'-flap structure1 Publication
  4. KM=3.45 nM for a nicked duplex1 Publication
  5. KM=14.0 nM for a regressed lagging strand replication fork1 Publication
  6. KM=245 nM for a Y structure1 Publication
  7. KM=173 nM for a double flap structure1 Publication
  1. Vmax=55.6 nmol/min/ng enzyme with a nicked Holliday junction as substrate1 Publication
  2. Vmax=31.3 nmol/min/ng enzyme with a regressed leading strand replication fork as substrate1 Publication
  3. Vmax=24.4 nmol/min/ng enzyme with a 3'-flap structure as substrate1 Publication
  4. Vmax=2.21 nmol/min/ng enzyme with a nicked duplex as substrate1 Publication
  5. Vmax=0.832 nmol/min/ng enzyme with a regressed lagging strand replication fork as subsystrate1 Publication
  6. Vmax=0.0468 nmol/min/ng enzyme with a Y structure as substrate1 Publication
  7. Vmax=0.0879 nmol/min/ng enzyme with a double flap structure as substrate1 Publication

pH dependencei

Optimum pH is 8.0 for cleavage of a 3'-flap structure.1 Publication

GO - Molecular functioni

GO - Biological processi

  • cellular response to DNA damage stimulus Source: SGD
  • DNA repair Source: SGD
  • DNA topological change Source: SGD
  • reciprocal meiotic recombination Source: SGD
  • regulation of reciprocal meiotic recombination Source: SGD
  • resolution of meiotic recombination intermediates Source: SGD
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Hydrolase, Nuclease

Keywords - Biological processi

DNA damage, DNA recombination, DNA repair, Meiosis

Keywords - Ligandi

Magnesium, Manganese, Metal-binding

Enzyme and pathway databases

BioCyciYEAST:G3O-29062-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Crossover junction endonuclease MMS4 (EC:3.1.22.-)
Gene namesi
Name:MMS4
Synonyms:SLX2
Ordered Locus Names:YBR098W
ORF Names:YBR0826, YBR0829, YBR100W
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
ProteomesiUP000002311 Componenti: Chromosome II

Organism-specific databases

CYGDiYBR098w.
EuPathDBiFungiDB:YBR098W.
SGDiS000000302. MMS4.

Subcellular locationi

  • Nucleus 1 Publication

GO - Cellular componenti

  • Holliday junction resolvase complex Source: SGD
  • nucleus Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi173 – 1731G → R in allele MMS4-1; loss of activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 691690Crossover junction endonuclease MMS4PRO_0000096516Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication
Modified residuei48 – 481Phosphoserine1 Publication
Modified residuei49 – 491Phosphoserine1 Publication
Modified residuei61 – 611Phosphoserine1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP38257.
PaxDbiP38257.
PeptideAtlasiP38257.
PRIDEiP38257.

Interactioni

Subunit structurei

Interacts with MUS81.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MUS81Q041493EBI-21547,EBI-33508

Protein-protein interaction databases

BioGridi32804. 127 interactions.
DIPiDIP-2927N.
IntActiP38257. 6 interactions.
MINTiMINT-603238.

Structurei

3D structure databases

ProteinModelPortaliP38257.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni598 – 69194Interaction with MUS81Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili364 – 39128Sequence AnalysisAdd
BLAST
Coiled coili507 – 52923Sequence AnalysisAdd
BLAST

Sequence similaritiesi

Belongs to the EME1/MMS4 family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiNOG40733.
HOGENOMiHOG000113612.
InParanoidiP38257.
OMAiSHMEFIN.
OrthoDBiEOG7FJHB5.

Family and domain databases

InterProiIPR006166. ERCC4_domain.
[Graphical view]
PfamiPF02732. ERCC4. 1 hit.
[Graphical view]
SMARTiSM00891. ERCC4. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P38257-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSQIVDFVED KDSRNDASIQ IIDGPSNVEI IALSESMDQD ECKRAHVSSA
60 70 80 90 100
EMIPSSPQRK SVSNDVENVD LNKSIELSAP FFQDISISKL DDFSTTVNSI
110 120 130 140 150
IDSSLRNENN AKGNAKKLLD DLISDEWSAD LESSGKKHNK SQYNLRDIAE
160 170 180 190 200
KWGVQSLKNP EPIAVDCEYK TQGIGKTNSD ISDSPKSQIG AADILFDFPL
210 220 230 240 250
SPVKHENPTE EKHNSIANEN SSPDNSLKPA GKQNHGEDGT SMAKRVYNKG
260 270 280 290 300
EDEQEHLPKG KKRTIALSRT LINSTKLPDT VELNLSKFLD SSDSITTDVL
310 320 330 340 350
STPAKGSNIV RTGSQPIFSN ANCFQEAKRS KTLTAEDPKC TKNTAREVSQ
360 370 380 390 400
LENYIAYGQY YTREDSKNKI RHLLKENKNA FKRVNQIYRD NIKARSQMII
410 420 430 440 450
EFSPSLLQLF KKGDSDLQQQ LAPAVVQSSY NDSMPLLRFL RKCDSIYDFS
460 470 480 490 500
NDFYYPCDPK IVEENVLILY YDAQEFFEQY TSQKKELYRK IRFFSKNGKH
510 520 530 540 550
VILILSDINK LKRAIFQLEN EKYKARVEQR LSGTEEALRP RSKKSSQVGK
560 570 580 590 600
LGIKKFDLEQ RLRFIDREWH VKIHTVNSHM EFINSLPNLV SLIGKQRMDP
610 620 630 640 650
AIRYMKYAHL NVKSAQDSTE TLKKTFHQIG RMPEMKANNV VSLYPSFQSL
660 670 680 690
LEDIEKGRLQ SDNEGKYLMT EAVEKRLYKL FTCTDPNDTI E
Length:691
Mass (Da):78,764
Last modified:April 13, 2004 - v2
Checksum:i3B3918DD3B2E7E0C
GO

Sequence cautioni

The sequence AAT92950.1 differs from that shown. Reason: Frameshift at position 466. Curated
The sequence CAA55603.1 differs from that shown. Reason: Frameshift at position 466. Curated
The sequence CAA85051.1 differs from that shown. Reason: Frameshift at position 466. Curated
The sequence CAA85054.1 differs from that shown. Reason: Erroneous initiation. Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14000 Genomic DNA. Translation: AAF06816.1.
X78993 Genomic DNA. Translation: CAA55603.1. Frameshift.
Z35967 Genomic DNA. Translation: CAA85051.1. Frameshift.
Z35968 Genomic DNA. Translation: CAA85054.1. Different initiation.
AY692931 Genomic DNA. Translation: AAT92950.1. Frameshift.
BK006936 Genomic DNA. Translation: DAA07219.1.
PIRiS45968.
S48265.
RefSeqiNP_009656.2. NM_001178446.1.

Genome annotation databases

EnsemblFungiiYBR098W; YBR098W; YBR098W.
GeneIDi852395.
KEGGisce:YBR098W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14000 Genomic DNA. Translation: AAF06816.1.
X78993 Genomic DNA. Translation: CAA55603.1. Frameshift.
Z35967 Genomic DNA. Translation: CAA85051.1. Frameshift.
Z35968 Genomic DNA. Translation: CAA85054.1. Different initiation.
AY692931 Genomic DNA. Translation: AAT92950.1. Frameshift.
BK006936 Genomic DNA. Translation: DAA07219.1.
PIRiS45968.
S48265.
RefSeqiNP_009656.2. NM_001178446.1.

3D structure databases

ProteinModelPortaliP38257.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi32804. 127 interactions.
DIPiDIP-2927N.
IntActiP38257. 6 interactions.
MINTiMINT-603238.

Proteomic databases

MaxQBiP38257.
PaxDbiP38257.
PeptideAtlasiP38257.
PRIDEiP38257.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYBR098W; YBR098W; YBR098W.
GeneIDi852395.
KEGGisce:YBR098W.

Organism-specific databases

CYGDiYBR098w.
EuPathDBiFungiDB:YBR098W.
SGDiS000000302. MMS4.

Phylogenomic databases

eggNOGiNOG40733.
HOGENOMiHOG000113612.
InParanoidiP38257.
OMAiSHMEFIN.
OrthoDBiEOG7FJHB5.

Enzyme and pathway databases

BioCyciYEAST:G3O-29062-MONOMER.

Miscellaneous databases

NextBioi971222.
PROiP38257.

Family and domain databases

InterProiIPR006166. ERCC4_domain.
[Graphical view]
PfamiPF02732. ERCC4. 1 hit.
[Graphical view]
SMARTiSM00891. ERCC4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mms4, a putative transcriptional (co)activator, protects Saccharomyces cerevisiae cells from endogenous and environmental DNA damage."
    Xiao W., Chow B.L., Milo C.N.
    Mol. Gen. Genet. 257:614-623(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], MUTAGENESIS OF GLY-173.
    Strain: S288c / GRF88.
  2. "Analysis of a 70 kb region on the right arm of yeast chromosome II."
    Mannhaupt G., Stucka R., Ehnle S., Vetter I., Feldmann H.
    Yeast 10:1363-1381(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  3. "Complete DNA sequence of yeast chromosome II."
    Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C., Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M., Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M., Cziepluch C.
    , Demolis N., Delaveau T., Doignon F., Domdey H., Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D., Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N., Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J., Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C., Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P., Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y., Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F., Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E., Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M., Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B., Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L., Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M., Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S., Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K., Mewes H.-W., Kleine K.
    EMBO J. 13:5795-5809(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  4. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.
  5. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  6. "Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease."
    Kaliraman V., Mullen J.R., Fricke W.M., Bastin-Shanower S.A., Brill S.J.
    Genes Dev. 15:2730-2740(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PROCESSING OF STALLED REPLICATION FORK, INTERACTION WITH MUS81.
  7. "Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae."
    Mullen J.R., Kaliraman V., Ibrahim S.S., Brill S.J.
    Genetics 157:103-118(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MUS81.
  8. "A role for MMS4 in the processing of recombination intermediates during meiosis in Saccharomyces cerevisiae."
    de los Santos T., Loidl J., Larkin B., Hollingsworth N.M.
    Genetics 159:1511-1525(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication."
    Fabre F., Chan A., Heyer W.-D., Gangloff S.
    Proc. Natl. Acad. Sci. U.S.A. 99:16887-16892(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. Erratum
    Fabre F., Chan A., Heyer W.-D., Gangloff S.
    Proc. Natl. Acad. Sci. U.S.A. 100:1462-1462(2002)
  11. "Functional domains required for the Saccharomyces cerevisiae Mus81-Mms4 endonuclease complex formation and nuclear localization."
    Fu Y., Xiao W.
    DNA Repair 2:1435-1447(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MUS81, SUBCELLULAR LOCATION, CHARACTERIZATION OF MUTANT ARG-173.
  12. "The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast."
    de los Santos T., Hunter N., Lee C., Larkin B., Loidl J., Hollingsworth N.M.
    Genetics 164:81-94(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CROSSOVER WITHOUT DOUBLE HOLLIDAY JUNCTION.
  13. "Cleavage of model replication forks by fission yeast Mus81-Eme1 and budding yeast Mus81-Mms4."
    Whitby M.C., Osman F., Dixon J.
    J. Biol. Chem. 278:6928-6935(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. "The mechanism of Mus81-Mms4 cleavage site selection distinguishes it from the homologous endonuclease Rad1-Rad10."
    Bastin-Shanower S.A., Fricke W.M., Mullen J.R., Brill S.J.
    Mol. Cell. Biol. 23:3487-3496(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CLEAVAGE SITE SELECTION.
  15. "Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis."
    Osman F., Dixon J., Doe C.L., Whitby M.C.
    Mol. Cell 12:761-774(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CROSSOVER WITHOUT DOUBLE HOLLIDAY JUNCTION.
  16. "Competing crossover pathways act during meiosis in Saccharomyces cerevisiae."
    Argueso J.L., Wanat J., Gemici Z., Alani E.
    Genetics 168:1805-1816(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  17. "Substrate specificity of the Saccharomyces cerevisiae Mus81-Mms4 endonuclease."
    Fricke W.M., Bastin-Shanower S.A., Brill S.J.
    DNA Repair 4:243-251(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH MUS81.
  18. "The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions."
    Hollingsworth N.M., Brill S.J.
    Genes Dev. 18:117-125(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  19. "A multidimensional chromatography technology for in-depth phosphoproteome analysis."
    Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.
    Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  20. "Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution."
    Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.
    Science 325:1682-1686(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; SER-49 AND SER-61, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  21. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiMMS4_YEAST
AccessioniPrimary (citable) accession number: P38257
Secondary accession number(s): D6VQ99
, P38259, Q6B1Z9, Q9URQ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: April 13, 2004
Last modified: July 22, 2015
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Two distinct classes of meiotic crossovers have been demonstrated in budding yeast. Class I crossovers exhibit crossover interference and require MSH4 and MSH5 for their resolution, while class II crossovers exhibit no crossover interference and require MUS81 and MMS4. While class I crossovers represent the majority of crossovers in S.cerevisiae, they are virtually absent in S.pombe which lacks orthologs of MSH4 and MSH5.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  3. Yeast chromosome II
    Yeast (Saccharomyces cerevisiae) chromosome II: entries and gene names

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.