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P38257 (MMS4_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Crossover junction endonuclease MMS4

EC=3.1.22.-
Gene names
Name:MMS4
Synonyms:SLX2
Ordered Locus Names:YBR098W
ORF Names:YBR0826, YBR0829, YBR100W
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length691 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17

Cofactor

Magnesium or manganese. Ref.17

Subunit structure

Interacts with MUS81. Ref.6 Ref.7 Ref.11 Ref.17

Subcellular location

Nucleus Ref.11.

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.

Sequence similarities

Belongs to the EME1/MMS4 family.

Biophysicochemical properties

Kinetic parameters:

KM=31.1 nM for a nicked Holliday junction Ref.17

KM=6.84 nM for a regressed leading strand replication fork

KM=4.8 nM for for a 3'-flap structure

KM=3.45 nM for a nicked duplex

KM=14.0 nM for a regressed lagging strand replication fork

KM=245 nM for a Y structure

KM=173 nM for a double flap structure

Vmax=55.6 nmol/min/ng enzyme with a nicked Holliday junction as substrate

Vmax=31.3 nmol/min/ng enzyme with a regressed leading strand replication fork as substrate

Vmax=24.4 nmol/min/ng enzyme with a 3'-flap structure as substrate

Vmax=2.21 nmol/min/ng enzyme with a nicked duplex as substrate

Vmax=0.832 nmol/min/ng enzyme with a regressed lagging strand replication fork as subsystrate

Vmax=0.0468 nmol/min/ng enzyme with a Y structure as substrate

Vmax=0.0879 nmol/min/ng enzyme with a double flap structure as substrate

pH dependence:

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

Sequence caution

The sequence AAT92950.1 differs from that shown. Reason: Frameshift at position 466.

The sequence CAA55603.1 differs from that shown. Reason: Frameshift at position 466.

The sequence CAA85051.1 differs from that shown. Reason: Frameshift at position 466.

The sequence CAA85054.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processDNA damage
DNA recombination
DNA repair
Meiosis
   Cellular componentNucleus
   DomainCoiled coil
   LigandMagnesium
Manganese
Metal-binding
   Molecular functionEndonuclease
Hydrolase
Nuclease
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA catabolic process, endonucleolytic

Inferred from direct assay Ref.6PubMed 17363897. Source: GOC

DNA repair

Inferred from mutant phenotype Ref.1. Source: SGD

DNA topological change

Inferred from genetic interaction Ref.7. Source: SGD

cellular response to DNA damage stimulus

Inferred from mutant phenotype Ref.7. Source: SGD

reciprocal meiotic recombination

Inferred from mutant phenotype PubMed 18615017. Source: SGD

regulation of RNA biosynthetic process

Inferred from direct assay Ref.1. Source: GOC

regulation of reciprocal meiotic recombination

Inferred from genetic interaction PubMed 18691965. Source: SGD

resolution of meiotic recombination intermediates

Inferred from genetic interaction PubMed 18691964. Source: SGD

   Cellular_componentHolliday junction resolvase complex

Inferred from direct assay PubMed 17363897. Source: SGD

nucleus

Inferred from sequence or structural similarity Ref.1. Source: SGD

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: InterPro

endonuclease activity

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

transcription coactivator activity

Inferred from direct assay Ref.1. Source: SGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MUS81Q041493EBI-21547,EBI-33508

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.21
Chain2 – 691690Crossover junction endonuclease MMS4
PRO_0000096516

Regions

Region598 – 69194Interaction with MUS81
Coiled coil364 – 39128 Potential
Coiled coil507 – 52923 Potential

Amino acid modifications

Modified residue21N-acetylserine Ref.21
Modified residue481Phosphoserine Ref.20
Modified residue491Phosphoserine Ref.20
Modified residue611Phosphoserine Ref.20

Experimental info

Mutagenesis1731G → R in allele MMS4-1; loss of activity. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P38257 [UniParc].

Last modified April 13, 2004. Version 2.
Checksum: 3B3918DD3B2E7E0C

FASTA69178,764
        10         20         30         40         50         60 
MSQIVDFVED KDSRNDASIQ IIDGPSNVEI IALSESMDQD ECKRAHVSSA EMIPSSPQRK 

        70         80         90        100        110        120 
SVSNDVENVD LNKSIELSAP FFQDISISKL DDFSTTVNSI IDSSLRNENN AKGNAKKLLD 

       130        140        150        160        170        180 
DLISDEWSAD LESSGKKHNK SQYNLRDIAE KWGVQSLKNP EPIAVDCEYK TQGIGKTNSD 

       190        200        210        220        230        240 
ISDSPKSQIG AADILFDFPL SPVKHENPTE EKHNSIANEN SSPDNSLKPA GKQNHGEDGT 

       250        260        270        280        290        300 
SMAKRVYNKG EDEQEHLPKG KKRTIALSRT LINSTKLPDT VELNLSKFLD SSDSITTDVL 

       310        320        330        340        350        360 
STPAKGSNIV RTGSQPIFSN ANCFQEAKRS KTLTAEDPKC TKNTAREVSQ LENYIAYGQY 

       370        380        390        400        410        420 
YTREDSKNKI RHLLKENKNA FKRVNQIYRD NIKARSQMII EFSPSLLQLF KKGDSDLQQQ 

       430        440        450        460        470        480 
LAPAVVQSSY NDSMPLLRFL RKCDSIYDFS NDFYYPCDPK IVEENVLILY YDAQEFFEQY 

       490        500        510        520        530        540 
TSQKKELYRK IRFFSKNGKH VILILSDINK LKRAIFQLEN EKYKARVEQR LSGTEEALRP 

       550        560        570        580        590        600 
RSKKSSQVGK LGIKKFDLEQ RLRFIDREWH VKIHTVNSHM EFINSLPNLV SLIGKQRMDP 

       610        620        630        640        650        660 
AIRYMKYAHL NVKSAQDSTE TLKKTFHQIG RMPEMKANNV VSLYPSFQSL LEDIEKGRLQ 

       670        680        690 
SDNEGKYLMT EAVEKRLYKL FTCTDPNDTI E 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Saccharomyces Genome Database
Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases
Cited for: GENOME REANNOTATION.
Strain: ATCC 204508 / S288c.
[5]"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae."
Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. expand/collapse author list , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J.
Genome Res. 17:536-543(2007) [PubMed] [Europe PMC] [Abstract]
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]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS45968.
S48265.
RefSeqNP_009656.2. NM_001178446.1.

3D structure databases

ProteinModelPortalP38257.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid32804. 125 interactions.
DIPDIP-2927N.
IntActP38257. 6 interactions.
MINTMINT-603238.

Proteomic databases

PaxDbP38257.
PeptideAtlasP38257.
PRIDEP38257.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYBR098W; YBR098W; YBR098W.
GeneID852395.
KEGGsce:YBR098W.

Organism-specific databases

CYGDYBR098w.
SGDS000000302. MMS4.

Phylogenomic databases

eggNOGNOG40733.
HOGENOMHOG000113612.
OMAPFQFSDE.
OrthoDBEOG7FJHB5.

Enzyme and pathway databases

BioCycYEAST:G3O-29062-MONOMER.

Gene expression databases

GenevestigatorP38257.

Family and domain databases

InterProIPR006166. ERCC4_domain.
[Graphical view]
PfamPF02732. ERCC4. 1 hit.
[Graphical view]
SMARTSM00891. ERCC4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio971222.

Entry information

Entry nameMMS4_YEAST
AccessionPrimary (citable) accession number: P38257
Secondary accession number(s): D6VQ99 expand/collapse secondary AC list , P38259, Q6B1Z9, Q9URQ2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: April 13, 2004
Last modified: April 16, 2014
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome II

Yeast (Saccharomyces cerevisiae) chromosome II: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families