Q96NY9 (MUS81_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Crossover junction endonuclease MUS81
EC=3.1.22.-

Gene names

Name:

MUS81

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	551 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Nucleus › nucleolus. 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.

Ontologies

Keywords
Biological process	DNA damage DNA recombination DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Endonuclease Hydrolase Nuclease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW DNA repair Inferred from mutant phenotype Ref.15. Source: UniProtKB
Cellular_component	nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	3'-flap endonuclease activity Inferred from mutant phenotype Ref.14. Source: UniProtKB DNA binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EME1	Q96AY2	4	EBI-2370806,EBI-2370825
SLX4	Q8IY92	8	EBI-2370806,EBI-2370740

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 551

551

Crossover junction endonuclease MUS81

PRO_0000198858

Regions

Domain

270 – 372

103

ERCC4

Region

125 – 244

120

Interaction with BLM

Natural variations

Natural variant

37

1

R → H. Ref.1 Ref.2 Ref.3
Corresponds to variant rs13817 [ dbSNP | Ensembl ].

VAR_025340

Natural variant

115

1

S → F.
Corresponds to variant rs34381357 [ dbSNP | Ensembl ].

VAR_061988

Natural variant

180

1

R → P. Ref.1 Ref.2 Ref.3
Corresponds to variant rs545500 [ dbSNP | Ensembl ].

VAR_038521

Natural variant

189

1

L → F.
Corresponds to variant rs2298447 [ dbSNP | Ensembl ].

VAR_021990

Natural variant

350

1

R → W.
Corresponds to variant rs34891773 [ dbSNP | Ensembl ].

VAR_038522

Natural variant

481

1

Q → H.
Corresponds to variant rs765593 [ dbSNP | Ensembl ].

VAR_025341

Experimental info

Mutagenesis

306 – 307

2

GD → AE: Loss of activity. Ref.1 Ref.8

Mutagenesis

333 – 334

2

ER → AG: Loss of activity. Ref.1 Ref.8

Mutagenesis

338 – 339

2

DD → AA: Loss of activity. Ref.1 Ref.8

Secondary structure

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551

Helix Strand Turn

Details...

Beta strand

275 – 277

3

Turn

289 – 291

3

Helix

292 – 294

3

Beta strand

305 – 309

5

Beta strand

329 – 332

4

Turn

337 – 340

4

Helix

341 – 344

4

Beta strand

345 – 347

3

Helix

348 – 352

5

Turn

353 – 356

4

Turn

358 – 360

3

Beta strand

362 – 365

4

Beta strand

373 – 376

4

Helix

381 – 393

13

Helix

405 – 408

4

Helix

410 – 416

7

Turn

417 – 421

5

Turn

458 – 461

4

Helix

462 – 464

3

Turn

465 – 467

3

Turn

471 – 473

3

Helix

474 – 477

4

Turn

488 – 492

5

Beta strand

493 – 497

5

Helix

500 – 508

9

Helix

513 – 515

3

Turn

516 – 520

5

Turn

526 – 529

4

Helix

534 – 544

11

Sequences

	Sequence		Length	Mass (Da)
	Q96NY9 [UniParc]. Last modified February 5, 2008. Version 3. Checksum: D0F331CC2269D847	FASTA	551	61,173
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00289454.

RefSeq

NP_079404.3. NM_025128.4.

UniGene

Hs.288798.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZIX	X-ray	3.50	A	246-551	[»]

ProteinModelPortal

Q96NY9.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48630N.

IntAct

Q96NY9. 3 interactions.

STRING

9606.ENSP00000307853.

PTM databases

PhosphoSite

Q96NY9.

Polymorphism databases

DMDM

166898077.

Proteomic databases

PaxDb

Q96NY9.

PRIDE

Q96NY9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000308110; ENSP00000307853; ENSG00000172732.
ENST00000437855; ENSP00000387722; ENSG00000172732.

GeneID

80198.

KEGG

hsa:80198.

UCSC

uc001ofv.4. human.

Organism-specific databases

CTD

80198.

GeneCards

GC11P065627.

H-InvDB

HIX0009809.

HGNC

HGNC:29814. MUS81.

MIM

606591. gene.

neXtProt

NX_Q96NY9.

PharmGKB

PA134881809.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1948.

HOGENOM

HOG000113699.

HOVERGEN

HBG052538.

InParanoid

Q96NY9.

KO

K08991.

OMA

CGRLQRN.

OrthoDB

EOG43TZVC.

PhylomeDB

Q96NY9.

Gene expression databases

ArrayExpress

Q96NY9.

Bgee

Q96NY9.

CleanEx

HS_MUS81.

Genevestigator

Q96NY9.

GermOnline

ENSG00000172732. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.10130. 1 hit.

InterPro

IPR010996. DNA_pol_b-like_N.
IPR020819. DNA_repair_nuc_XPF/helicase.
IPR006166. ERCC4_domain.
IPR003583. Hlx-hairpin-Hlx_DNA-bd_motif.
IPR011335. Restrct_endonuc-II-like.
[Graphical view]

Pfam

PF02732. ERCC4. 1 hit.
[Graphical view]

SMART

SM00891. ERCC4. 1 hit.
SM00278. HhH1. 1 hit.
[Graphical view]

SUPFAM

SSF47802. DNApol_B_N_like. 1 hit.
SSF52980. Restrict_endonuc_II-like_core. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q96NY9.

GenomeRNAi

80198.

NextBio

70556.

SOURCE

Search...

Entry information

Entry name

MUS81_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 106 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.