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

    Gene ID: 80198, updated on 28-Oct-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)

    Genotypes

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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