Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q96NY9 (MUS81_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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 MUS81

EC=3.1.22.-
Gene names
Name:MUS81
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length551 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Interacts with EME1 and EME2 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, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication forks. Ref.1 Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.14 Ref.15

Cofactor

Magnesium. Ref.1

Subunit structure

May self-associate. Interacts with EME1, EME2 and CHEK2. Interacts with BLM, and this interaction may stimulate the endonuclease activity of MUS81. Interacts with SLX4/BTBD12; this interaction is direct and links the MUS81-EME1 complex to SLX4, which may coordinate the action of the structure-specific endonuclease during DNA repair. Interacts with DCLRE1B/Apollo. Ref.1 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.12 Ref.14 Ref.15 Ref.16

Subcellular location

Nucleusnucleolus. Note: Recruited to foci of DNA damage in S-phase cells. Ref.1 Ref.7 Ref.8 Ref.9

Tissue specificity

Widely expressed.

Developmental stage

Expressed in S phase and G2 phase. Ref.7

Induction

Up-regulated in cells treated with agents that damage DNA or block replication. This up-regulation seems to be independent of transcription. Ref.1

Sequence similarities

Belongs to the XPF family.

Contains 1 ERCC4 domain.

Sequence caution

The sequence BAB14953.1 differs from that shown. Reason: Erroneous initiation.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 551551Crossover junction endonuclease MUS81
PRO_0000198858

Regions

Domain270 – 372103ERCC4
Region125 – 244120Interaction with BLM

Natural variations

Natural variant371R → H. Ref.1 Ref.2 Ref.3
Corresponds to variant rs13817 [ dbSNP | Ensembl ].
VAR_025340
Natural variant1151S → F.
Corresponds to variant rs34381357 [ dbSNP | Ensembl ].
VAR_061988
Natural variant1801R → P. Ref.1 Ref.2 Ref.3
Corresponds to variant rs545500 [ dbSNP | Ensembl ].
VAR_038521
Natural variant1891L → F.
Corresponds to variant rs2298447 [ dbSNP | Ensembl ].
VAR_021990
Natural variant3501R → W.
Corresponds to variant rs34891773 [ dbSNP | Ensembl ].
VAR_038522
Natural variant4811Q → H.
Corresponds to variant rs765593 [ dbSNP | Ensembl ].
VAR_025341

Experimental info

Mutagenesis306 – 3072GD → AE: Loss of activity. Ref.1 Ref.8
Mutagenesis333 – 3342ER → AG: Loss of activity. Ref.1 Ref.8
Mutagenesis338 – 3392DD → AA: Loss of activity. Ref.1 Ref.8

Secondary structure

................................................................... 551
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q96NY9 [UniParc].

Last modified February 5, 2008. Version 3.
Checksum: D0F331CC2269D847

FASTA55161,173
        10         20         30         40         50         60 
MAAPVRLGRK RPLPACPNPL FVRWLTEWRD EATRSRRRTR FVFQKALRSL RRYPLPLRSG 

        70         80         90        100        110        120 
KEAKILQHFG DGLCRMLDER LQRHRTSGGD HAPDSPSGEN SPAPQGRLAE VQDSSMPVPA 

       130        140        150        160        170        180 
QPKAGGSGSY WPARHSGARV ILLVLYREHL NPNGHHFLTK EELLQRCAQK SPRVAPGSAR 

       190        200        210        220        230        240 
PWPALRSLLH RNLVLRTHQP ARYSLTPEGL ELAQKLAESE GLSLLNVGIG PKEPPGEETA 

       250        260        270        280        290        300 
VPGAASAELA SEAGVQQQPL ELRPGEYRVL LCVDIGETRG GGHRPELLRE LQRLHVTHTV 

       310        320        330        340        350        360 
RKLHVGDFVW VAQETNPRDP ANPGELVLDH IVERKRLDDL CSSIIDGRFR EQKFRLKRCG 

       370        380        390        400        410        420 
LERRVYLVEE HGSVHNLSLP ESTLLQAVTN TQVIDGFFVK RTADIKESAA YLALLTRGLQ 

       430        440        450        460        470        480 
RLYQGHTLRS RPWGTPGNPE SGAMTSPNPL CSLLTFSDFN AGAIKNKAQS VREVFARQLM 

       490        500        510        520        530        540 
QVRGVSGEKA AALVDRYSTP ASLLAAYDAC ATPKEQETLL STIKCGRLQR NLGPALSRTL 

       550 
SQLYCSYGPL T 

« Hide

References

« Hide 'large scale' references
[1]"Human Mus81-associated endonuclease cleaves Holliday junctions in vitro."
Chen X.-B., Melchionna R., Denis C.-M., Gaillard P.-H.L., Blasina A., Van de Weyer I., Boddy M.N., Russell P., Vialard J., McGowan C.H.
Mol. Cell 8:1117-1127(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-37 AND PRO-180, FUNCTION, COFACTOR, INTERACTION WITH CHEK2, SUBCELLULAR LOCATION, INDUCTION, MUTAGENESIS OF 306-GLY-ASP-307; 333-GLU-ARG-334 AND 338-ASP-ASP-339.
Tissue: Cerebellum.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS HIS-37 AND PRO-180.
Tissue: Brain.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 24-551, VARIANTS HIS-37 AND PRO-180.
[4]"Holliday junction resolution in human cells: two junction endonucleases with distinct substrate specificities."
Constantinou A., Chen X.-B., McGowan C.H., West S.C.
EMBO J. 21:5577-5585(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Identification and characterization of human MUS81-MMS4 structure-specific endonuclease."
Oegruenc M., Sancar A.
J. Biol. Chem. 278:21715-21720(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EME1.
[6]"Identification and characterization of the human mus81-eme1 endonuclease."
Ciccia A., Constantinou A., West S.C.
J. Biol. Chem. 278:25172-25178(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EME1.
[7]"Mus81 endonuclease localizes to nucleoli and to regions of DNA damage in human S-phase cells."
Gao H., Chen X.-B., McGowan C.H.
Mol. Biol. Cell 14:4826-4834(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[8]"RNA interference inhibition of Mus81 reduces mitotic recombination in human cells."
Blais V., Gao H., Elwell C.A., Boddy M.N., Gaillard P.-H.L., Russell P., McGowan C.H.
Mol. Biol. Cell 15:552-562(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SELF-ASSOCIATION, INTERACTION WITH EME1, SUBCELLULAR LOCATION, MUTAGENESIS OF 338-ASP-ASP-339.
[9]"BLM helicase facilitates Mus81 endonuclease activity in human cells."
Zhang R., Sengupta S., Yang Q., Linke S.P., Yanaihara N., Bradsher J., Blais V., McGowan C.H., Harris C.C.
Cancer Res. 65:2526-2531(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BLM, SUBCELLULAR LOCATION.
[10]"Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM."
Ciccia A., Ling C., Coulthard R., Yan Z., Xue Y., Meetei A.R., Laghmani el H., Joenje H., McDonald N., de Winter J.P., Wang W., West S.C.
Mol. Cell 25:331-343(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EME1 AND EME2.
[11]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint activation in response to DNA interstrand cross-links."
Bae J.B., Mukhopadhyay S.S., Liu L., Zhang N., Tan J., Akhter S., Liu X., Shen X., Li L., Legerski R.J.
Oncogene 27:5045-5056(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DCLRE1B.
[13]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair."
Munoz I.M., Hain K., Declais A.-C., Gardiner M., Toh G.W., Sanchez-Pulido L., Heuckmann J.M., Toth R., Macartney T., Eppink B., Kanaar R., Ponting C.P., Lilley D.M.J., Rouse J.
Mol. Cell 35:116-127(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SLX4.
[15]"Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair."
Svendsen J.M., Smogorzewska A., Sowa M.E., O'Connell B.C., Gygi S.P., Elledge S.J., Harper J.W.
Cell 138:63-77(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SLX4.
[16]"Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases."
Fekairi S., Scaglione S., Chahwan C., Taylor E.R., Tissier A., Coulon S., Dong M.-Q., Ruse C., Yates J.R. III, Russell P., Fuchs R.P., McGowan C.H., Gaillard P.-H.L.
Cell 138:78-89(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLX4.
[17]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF425646 mRNA. Translation: AAL28065.1.
BC009999 mRNA. Translation: AAH09999.2.
AK024665 mRNA. Translation: BAB14953.1. Different initiation.
RefSeqNP_079404.3. NM_025128.4.
UniGeneHs.288798.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2MC3NMR-A127-230[»]
2ZIXX-ray3.50A246-551[»]
ProteinModelPortalQ96NY9.
SMRQ96NY9. Positions 11-90, 128-230, 259-551.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123170. 11 interactions.
DIPDIP-48630N.
IntActQ96NY9. 6 interactions.
MINTMINT-3056813.
STRING9606.ENSP00000307853.

PTM databases

PhosphoSiteQ96NY9.

Polymorphism databases

DMDM166898077.

Proteomic databases

PaxDbQ96NY9.
PRIDEQ96NY9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000308110; ENSP00000307853; ENSG00000172732.
GeneID80198.
KEGGhsa:80198.
UCSCuc001ofv.4. human.

Organism-specific databases

CTD80198.
GeneCardsGC11P065627.
H-InvDBHIX0009809.
HGNCHGNC:29814. MUS81.
HPAHPA050711.
HPA059530.
MIM606591. gene.
neXtProtNX_Q96NY9.
PharmGKBPA134881809.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1948.
HOGENOMHOG000113699.
HOVERGENHBG052538.
InParanoidQ96NY9.
KOK08991.
OMAKCGRLQR.
OrthoDBEOG7TXKGV.
PhylomeDBQ96NY9.
TreeFamTF315113.

Gene expression databases

ArrayExpressQ96NY9.
BgeeQ96NY9.
CleanExHS_MUS81.
GenevestigatorQ96NY9.

Family and domain databases

Gene3D1.10.8.310. 1 hit.
3.40.50.10130. 1 hit.
InterProIPR010996. DNA_pol_b-like_N.
IPR020819. DNA_repair_nuc_XPF/helicase.
IPR006166. ERCC4_domain.
IPR003583. Hlx-hairpin-Hlx_DNA-bd_motif.
IPR027420. PolB_N.
IPR011335. Restrct_endonuc-II-like.
[Graphical view]
PfamPF02732. ERCC4. 1 hit.
[Graphical view]
SMARTSM00891. ERCC4. 1 hit.
SM00278. HhH1. 1 hit.
[Graphical view]
SUPFAMSSF47802. SSF47802. 1 hit.
SSF52980. SSF52980. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ96NY9.
GeneWikiMUS81.
GenomeRNAi80198.
NextBio70556.
PROQ96NY9.
SOURCESearch...

Entry information

Entry nameMUS81_HUMAN
AccessionPrimary (citable) accession number: Q96NY9
Secondary accession number(s): Q9H7D9
Entry history
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: February 5, 2008
Last modified: April 16, 2014
This is version 114 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM