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MUS81 MUS81 structure-specific endonuclease subunit [ Homo sapiens (human) ]

Gene ID: 80198, updated on 2-Nov-2024

Summary

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Official Symbol
MUS81provided by HGNC
Official Full Name
MUS81 structure-specific endonuclease subunitprovided by HGNC
Primary source
HGNC:HGNC:29814
See related
Ensembl:ENSG00000172732 MIM:606591; AllianceGenome:HGNC:29814
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SLX3
Summary
This gene encodes a structure-specific endonuclease which belongs to the XPF/MUS81 endonuclease family and plays a critical role in the resolution of recombination intermediates during DNA repair after inter-strand cross-links, replication fork collapse, and DNA double-strand breaks. The encoded protein associates with one of two closely related essential meiotic endonuclease proteins (EME1 or EME2) to form a complex that processes DNA secondary structures. It contains an N-terminal DEAH helicase domain, an excision repair cross complementation group 4 (ERCC4) endonuclease domain, and two tandem C-terminal helix-hairpin-helix domains. Mice with a homozygous knockout of the orthologous gene have significant meiotic defects including the failure to repair a subset of DNA double strand breaks. [provided by RefSeq, Jun 2017]
Expression
Ubiquitous expression in spleen (RPKM 12.7), endometrium (RPKM 11.9) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See MUS81 in Genome Data Viewer
Location:
11q13.1
Exon count:
19
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (65859674..65867653)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (65854904..65862125)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (65627904..65635124)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chr11:65601289-65601501 Neighboring gene sorting nexin 32 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5009 Neighboring gene Sharpr-MPRA regulatory region 3467 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:65618925-65619786 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5010 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5011 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:65625223-65625763 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5013 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5014 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3560 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5015 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5016 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:65627927-65628466 Neighboring gene cofilin 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3562 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:65629159-65629672 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:65632825-65633326 Neighboring gene EGF containing fibulin extracellular matrix protein 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3563 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5017 Neighboring gene cathepsin W Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5018 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3564 Neighboring gene FGF1 intracellular binding protein Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3565 Neighboring gene coiled-coil domain containing 85B

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Holliday junction processing enzymes as guardians of genome stability. Sarbajna S, et al. Trends Biochem Sci, 2014 Sep. PMID 25131815
  2. Feedback regulation of methyl methanesulfonate and ultraviolet-sensitive gene clone 81 via ATM/Chk2 pathway contributes to the resistance of MCF-7 breast cancer cells to cisplatin. Lv J, et al. Tumour Biol, 2017 Mar. PMID 28347251
  3. MUS81 nuclease activity is essential for replication stress tolerance and chromosome segregation in BRCA2-deficient cells. Lai X, et al. Nat Commun, 2017 Jul 17. PMID 28714477, Free PMC Article
  4. Mus81 knockdown sensitizes colon cancer cells to chemotherapeutic drugs by activating CHK1 pathway. Wu F, et al. Clin Res Hepatol Gastroenterol, 2017 Oct. PMID 28291626
  5. A Mechanism for Controlled Breakage of Under-replicated Chromosomes during Mitosis. Duda H, et al. Dev Cell, 2016 Dec 19. PMID 27997828

See all (140) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. DNA hypermethylation of tumor suppressor genes TWIST1, GATA4, MUS81 and NTRK1 in endometrial hyperplasia.
    Title: DNA hypermethylation of tumor suppressor genes TWIST1, GATA4, MUS81 and NTRK1 in endometrial hyperplasia.
  2. A study of protective effects of Mus81 in preeclampsia.
    Title: A study of protective effects of Mus81 in preeclampsia.
  3. Crystal structure of the human MUS81-EME2 complex.
    Title: Crystal structure of the human MUS81-EME2 complex.
  4. Mus81-Eme1-dependent aberrant processing of DNA replication intermediates in mitosis impairs genome integrity.
    Title: Mus81-Eme1-dependent aberrant processing of DNA replication intermediates in mitosis impairs genome integrity.
  5. Abraxas suppresses DNA end resection and limits break-induced replication by controlling SLX4/MUS81 chromatin loading in response to TOP1 inhibitor-induced DNA damage.
    Title: Abraxas suppresses DNA end resection and limits break-induced replication by controlling SLX4/MUS81 chromatin loading in response to TOP1 inhibitor-induced DNA damage.
  6. ATRX and RECQ5 define distinct homologous recombination subpathways.
    Title: ATRX and RECQ5 define distinct homologous recombination subpathways.
  7. Homologous recombination and Mus81 promote replication completion in response to replication fork blockage.
    Title: Homologous recombination and Mus81 promote replication completion in response to replication fork blockage.
  8. we show that Mus81 is a regulator of ZEB1 and promotes metastasis in gastric cancer. Importantly, we demonstrate that the BRD4 inhibitor AZD5153 can potentially be used as an effective antimetastasis drug because of its effect on Mus81.
    Title: The DNA Endonuclease Mus81 Regulates ZEB1 Expression and Serves as a Target of BET4 Inhibitors in Gastric Cancer.
  9. In WRN-deficient cells, persistence of RAD51 correlates with elevated mitotic phosphorylation of MUS81 at Ser87, which is essential to prevent excessive mitotic abnormalities. Aberrant fork degradation, in the presence of a wild-type RAD51 axis, stimulates RAD51-mediated post-replicative repair and engagement of the MUS81 complex to limit genome instability and cell death.
    Title: RAD51 and mitotic function of mus81 are essential for recovery from low-dose of camptothecin in the absence of the WRN exonuclease.
  10. XPF and MUS81 merit further validation in prospective clinical trials as biomarkers that may predict clinical response of esophageal adenocarcinoma (EAC) to oxaliplatin-based chemotherapy.
    Title: Translational study identifies XPF and MUS81 as predictive biomarkers for oxaliplatin-based peri-operative chemotherapy in patients with esophageal adenocarcinoma.
Submit: New GeneRIF Correction See all GeneRIFs (62)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris.
EBI GWAS Catalog
Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of MUS81 endonuclease homolog (S. cerevisiae, MUS81) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

Protein interactions

Protein Gene Interaction Pubs
Vpr vpr HIV-1 Vpr downregulates MUS81 and its cofactor EME1 by hijacking the host CRL4-DCAF1 E3 ubiquitin ligase; this does not correlate with Vpr-induced G2 cell cycle arrest PubMed
vpr HIV-1 Vpr R80A mutant demonstrates decreased or absent TNF production from MT4C5 cells suggesting that MUS81-Vpr interaction affects TNF production from HIV-1 infected cells PubMed
vpr HIV-1 Vpr-mediated cell cycle G2/M arrest requires human SLX4, MUS81, and EME1 proteins in cells PubMed
vpr HIV-1 Vpr mutants Q65R and R80A are deficient in G2 arrest induction, but degrade MUS81 to a similar degree as does wild-type Vpr, suggesting an independent G2-arrest pathway for Vpr-induced MUS81 degradation PubMed
vpr VPRBP is required for HIV-1 Vpr-mediated activation of the SLX4 complex and modulation of MUS81 levels. The interaction between Vpr and VPRBP is involved in MUS81 ubiquitination PubMed
vpr HIV-1 Vpr induces untimely activation of SLX4-associated MUS81-EME1 through phosphorylation of EME1 by PLK1 PubMed
vpr Co-immunoprecipitation and glycerol-gradient sedimentation demonstrate that HIV-1 Vpr, VPRBP, DDB1, SLX4, MUS81, EME1, ERCC1, and ERCC4 form a complex PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ21012, FLJ44872

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 3'-flap endonuclease activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables 3'-flap endonuclease activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables DNA binding IEA
Inferred from Electronic Annotation
more info
  
contributes_to crossover junction DNA endonuclease activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables endonuclease activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
acts_upstream_of_or_within DNA catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in DNA repair IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in double-strand break repair IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in double-strand break repair via break-induced replication IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mitotic intra-S DNA damage checkpoint signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in osteoblast proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in replication fork processing IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in resolution of meiotic recombination intermediates IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within response to intra-S DNA damage checkpoint signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
part_of Holliday junction resolvase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of endodeoxyribonuclease complex IPI
Inferred from Physical Interaction
more info
 PubMed 
located_in nuclear replication fork NAS
Non-traceable Author Statement
more info
 PubMed 
located_in nucleolus IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in replication fork IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
crossover junction endonuclease MUS81
Names
MUS81 endonuclease homolog
SLX3 structure-specific endonuclease subunit homolog
NP_001337212.1
NP_079404.3
XP_011543571.1
XP_011543572.1
XP_047283591.1
XP_047283592.1
XP_047283593.1
XP_047283594.1
XP_054226015.1
XP_054226016.1
XP_054226017.1
XP_054226018.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_053116.1 RefSeqGene

    Range
    5372..11378
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001350283.2 → NP_001337212.1  crossover junction endonuclease MUS81 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AK223564, BC009999, BI816797, CR989527, DA449863
    UniProtKB/TrEMBL
    B3KX63, Q53ES5
    Conserved Domains (2) summary
    pfam02732
    Location:273 → 416
    ERCC4; ERCC4 domain
    pfam14716
    Location:43 → 79
    HHH_8; Helix-hairpin-helix domain

  2. NM_025128.5 → NP_079404.3  crossover junction endonuclease MUS81 isoform 2

    See identical proteins and their annotated locations for NP_079404.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AK223564, BC009999, BI816797, DA449863
    Consensus CDS
    CCDS8115.1
    UniProtKB/Swiss-Prot
    Q96NY9, Q9H7D9
    UniProtKB/TrEMBL
    B3KX63, Q53ES5
    Related
    ENSP00000307853.4, ENST00000308110.9
    Conserved Domains (2) summary
    COG1948
    Location:261 → 515
    MUS81; ERCC4-type nuclease [Replication, recombination and repair]
    pfam02732
    Location:273 → 415
    ERCC4; ERCC4 domain

RNA

  1. NR_146598.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses two alternate splice sites and has an alternate 3' exon structure, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AP001201, AP001266, BI334628

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    65859674..65867653
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011545269.2 → XP_011543571.1  crossover junction endonuclease MUS81 isoform X1

    See identical proteins and their annotated locations for XP_011543571.1

    UniProtKB/TrEMBL
    B3KX63, Q53ES5
    Conserved Domains (2) summary
    pfam02732
    Location:273 → 416
    ERCC4; ERCC4 domain
    pfam14716
    Location:43 → 79
    HHH_8; Helix-hairpin-helix domain

  2. XM_011545270.2 → XP_011543572.1  crossover junction endonuclease MUS81 isoform X2

    See identical proteins and their annotated locations for XP_011543572.1

    UniProtKB/Swiss-Prot
    Q96NY9, Q9H7D9
    UniProtKB/TrEMBL
    B3KX63, Q53ES5
    Related
    ENSP00000432287.1, ENST00000533035.5
    Conserved Domains (2) summary
    COG1948
    Location:261 → 515
    MUS81; ERCC4-type nuclease [Replication, recombination and repair]
    pfam02732
    Location:273 → 415
    ERCC4; ERCC4 domain

  3. XM_047427635.1 → XP_047283591.1  crossover junction endonuclease MUS81 isoform X3

  4. XM_047427637.1 → XP_047283593.1  crossover junction endonuclease MUS81 isoform X5

  5. XM_047427638.1 → XP_047283594.1  crossover junction endonuclease MUS81 isoform X5

  6. XM_047427636.1 → XP_047283592.1  crossover junction endonuclease MUS81 isoform X4

    Related
    ENSP00000433473.1, ENST00000524647.5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    65854904..65862125
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054370041.1 → XP_054226016.1  crossover junction endonuclease MUS81 isoform X4

  2. XM_054370040.1 → XP_054226015.1  crossover junction endonuclease MUS81 isoform X3

  3. XM_054370042.1 → XP_054226017.1  crossover junction endonuclease MUS81 isoform X5

  4. XM_054370043.1 → XP_054226018.1  crossover junction endonuclease MUS81 isoform X5

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96NY9.3 GenPept UniProtKB/Swiss-Prot:Q96NY9

Gene LinkOut

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