Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Crossover junction endonuclease MUS81

Gene

MUS81

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 MMS4 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 the cleavage of a 3'-flap structure.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei415 – 4151Curated

GO - Molecular functioni

  • DNA binding Source: InterPro
  • endonuclease activity Source: UniProtKB-KW
  • enzyme inhibitor activity Source: SGD
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • cellular response to DNA damage stimulus Source: SGD
  • DNA repair Source: SGD
  • DNA topological change Source: SGD
  • double-strand break repair via break-induced replication Source: SGD
  • negative regulation of helicase activity Source: SGD
  • 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-29934-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Crossover junction endonuclease MUS81 (EC:3.1.22.-)
Alternative name(s):
MMS and UV-sensitive protein 81
Gene namesi
Name:MUS81
Synonyms:SLX3
Ordered Locus Names:YDR386W
ORF Names:D9509.6
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome IV

Organism-specific databases

EuPathDBiFungiDB:YDR386W.
SGDiS000002794. MUS81.

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
Mutagenesisi414 – 4152DD → AA in allele MUS81-DD; abrogates endonuclease activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 632632Crossover junction endonuclease MUS81PRO_0000198861Add
BLAST

Proteomic databases

MaxQBiQ04149.
PeptideAtlasiQ04149.
PRIDEiQ04149.

PTM databases

iPTMnetiQ04149.

Interactioni

Subunit structurei

Interacts with MMS4 and RAD54.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MMS4P382573EBI-33508,EBI-21547

Protein-protein interaction databases

BioGridi32447. 137 interactions.
DIPiDIP-1009N.
IntActiQ04149. 7 interactions.
MINTiMINT-406845.

Structurei

3D structure databases

ProteinModelPortaliQ04149.
SMRiQ04149. Positions 132-229, 370-607.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini351 – 44898ERCC4Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni527 – 632106Interaction with MMS4Add
BLAST

Sequence similaritiesi

Belongs to the XPF family.Curated
Contains 1 ERCC4 domain.Curated

Phylogenomic databases

GeneTreeiENSGT00390000005498.
HOGENOMiHOG000248281.
InParanoidiQ04149.
KOiK08991.
OMAiGWIKEWL.
OrthoDBiEOG76MKJ6.

Family and domain databases

Gene3Di3.40.50.10130. 1 hit.
InterProiIPR010996. DNA_pol_b-like_N.
IPR020819. DNA_repair_nuc_XPF/helicase.
IPR006166. ERCC4_domain.
IPR033309. Mus81.
IPR011335. Restrct_endonuc-II-like.
[Graphical view]
PANTHERiPTHR13451:SF0. PTHR13451:SF0. 1 hit.
PfamiPF02732. ERCC4. 1 hit.
[Graphical view]
SMARTiSM00891. ERCC4. 1 hit.
[Graphical view]
SUPFAMiSSF47802. SSF47802. 1 hit.
SSF52980. SSF52980. 1 hit.

Sequencei

Sequence statusi: Complete.

Q04149-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELSSNLKDL YIEWLQELVD GLTPKQEQLK IAYEKAKRNL QNAEGSFYYP
60 70 80 90 100
TDLKKVKGIG NTIIKRLDTK LRNYCKIHHI SPVEAPSLTQ TSSTRPPKRT
110 120 130 140 150
TTALRSIVNS CENDKNEAPE EKGTKKRKTR KYIPKKRSGG YAILLSLLEL
160 170 180 190 200
NAIPRGVSKE QIIEVAGKYS DHCMTPNFST KEFYGAWSSI AALKKHSLVL
210 220 230 240 250
EEGRPKRYSL TEEGVELTKS LKTADGISFP KENEEPNEYS VTRNESSEFT
260 270 280 290 300
ANLTDLRGEY GKEEEPCDIN NTSFMLDITF QDLSTPQRLQ NNVFKNDRLN
310 320 330 340 350
SQTNISSHKL EEVSDDQTVP DSALKAKSTI KRRRYNGVSY ELWCSGDFEV
360 370 380 390 400
FPIIDHREIK SQSDREFFSR AFERKGMKSE IRQLALGDII WVAKNKNTGL
410 420 430 440 450
QCVLNTIVER KRLDDLALSI RDNRFMEQKN RLEKSGCEHK YYLIEETMSG
460 470 480 490 500
NIGNMNEALK TALWVILVYY KFSMIRTCNS DETVEKIHAL HTVISHHYSQ
510 520 530 540 550
KDLIVIFPSD LKSKDDYKKV LLQFRREFER KGGIECCHNL ECFQELMGKG
560 570 580 590 600
DLKTVGELTI HVLMLVKGIS LEKAVAIQEI FPTLNKILMA YKTCSSEEEA
610 620 630
KLLMFNVLGD APGAKKITKS LSEKIYDAFG KL
Length:632
Mass (Da):72,309
Last modified:November 1, 1996 - v1
Checksum:iF73FA3856C5F87F1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U32274 Genomic DNA. Translation: AAB64828.1.
BK006938 Genomic DNA. Translation: DAA12230.1.
PIRiS69670.
RefSeqiNP_010674.3. NM_001180694.3.

Genome annotation databases

EnsemblFungiiYDR386W; YDR386W; YDR386W.
GeneIDi851994.
KEGGisce:YDR386W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U32274 Genomic DNA. Translation: AAB64828.1.
BK006938 Genomic DNA. Translation: DAA12230.1.
PIRiS69670.
RefSeqiNP_010674.3. NM_001180694.3.

3D structure databases

ProteinModelPortaliQ04149.
SMRiQ04149. Positions 132-229, 370-607.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi32447. 137 interactions.
DIPiDIP-1009N.
IntActiQ04149. 7 interactions.
MINTiMINT-406845.

PTM databases

iPTMnetiQ04149.

Proteomic databases

MaxQBiQ04149.
PeptideAtlasiQ04149.
PRIDEiQ04149.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYDR386W; YDR386W; YDR386W.
GeneIDi851994.
KEGGisce:YDR386W.

Organism-specific databases

EuPathDBiFungiDB:YDR386W.
SGDiS000002794. MUS81.

Phylogenomic databases

GeneTreeiENSGT00390000005498.
HOGENOMiHOG000248281.
InParanoidiQ04149.
KOiK08991.
OMAiGWIKEWL.
OrthoDBiEOG76MKJ6.

Enzyme and pathway databases

BioCyciYEAST:G3O-29934-MONOMER.

Miscellaneous databases

PROiQ04149.

Family and domain databases

Gene3Di3.40.50.10130. 1 hit.
InterProiIPR010996. DNA_pol_b-like_N.
IPR020819. DNA_repair_nuc_XPF/helicase.
IPR006166. ERCC4_domain.
IPR033309. Mus81.
IPR011335. Restrct_endonuc-II-like.
[Graphical view]
PANTHERiPTHR13451:SF0. PTHR13451:SF0. 1 hit.
PfamiPF02732. ERCC4. 1 hit.
[Graphical view]
SMARTiSM00891. ERCC4. 1 hit.
[Graphical view]
SUPFAMiSSF47802. SSF47802. 1 hit.
SSF52980. SSF52980. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV."
    Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., Delaveau T.
    , del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L., Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H., Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M., Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M., Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A., Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G., Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E., Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S., Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D., Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V., Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E., Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X., Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A., Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T., Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L., Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E., Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L., Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M., Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K., Mewes H.-W., Zollner A., Zaccaria P.
    Nature 387:75-78(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  2. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.
  3. "MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae."
    Interthal H., Heyer W.-D.
    Mol. Gen. Genet. 263:812-827(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DNA REPAIR, INTERACTION WITH RAD54.
  4. "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 MMS4.
  5. "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 MMS4.
  6. "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.
  7. Erratum
    Fabre F., Chan A., Heyer W.-D., Gangloff S.
    Proc. Natl. Acad. Sci. U.S.A. 100:1462-1462(2002)
  8. "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 MMS4, SUBCELLULAR LOCATION.
  9. "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, MUTAGENESIS OF 414-ASP-ASP-415.
  10. "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.
  11. "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.
  12. "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.
  13. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
  14. "Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae."
    Ii M., Brill S.J.
    Curr. Genet. 48:213-225(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  15. "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 MMS4.
  16. "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.
  17. "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].

Entry informationi

Entry nameiMUS81_YEAST
AccessioniPrimary (citable) accession number: Q04149
Secondary accession number(s): D6VT20
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: November 1, 1996
Last modified: June 8, 2016
This is version 135 of the entry and version 1 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.
Present with 300 molecules/cell in log phase SD medium.1 Publication

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

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 one 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.