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    Cop1 COP1, E3 ubiquitin ligase [ Mus musculus (house mouse) ]

    Gene ID: 26374, updated on 28-Oct-2024

    Summary

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    Official Symbol
    Cop1provided by MGI
    Official Full Name
    COP1, E3 ubiquitin ligaseprovided by MGI
    Primary source
    MGI:MGI:1347046
    See related
    Ensembl:ENSMUSG00000040782 AllianceGenome:MGI:1347046
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Rfwd2
    Summary
    Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; and response to ionizing radiation. Predicted to be located in Golgi membrane. Predicted to be part of Cul4A-RING E3 ubiquitin ligase complex. Is expressed in several structures, including central nervous system; genitourinary system; limb; and liver. Orthologous to human COP1 (COP1 E3 ubiquitin ligase). [provided by Alliance of Genome Resources, Oct 2024]
    Expression
    Ubiquitous expression in CNS E14 (RPKM 4.0), whole brain E14.5 (RPKM 4.0) and 28 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Cop1 in Genome Data Viewer
    Location:
    1 H1; 1 69.03 cM
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 1 NC_000067.7 (159059734..159182442)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 1 NC_000067.6 (159232156..159354872)

    Chromosome 1 - NC_000067.7Genomic Context describing neighboring genes Neighboring gene RIKEN cDNA 4930562F17 gene Neighboring gene STARR-positive B cell enhancer ABC_E9187 Neighboring gene ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d pseudogene Neighboring gene t-complex protein 11 pseudogene Neighboring gene POU domain, class 5, transcription factor 1, related sequence 1 Neighboring gene STARR-seq mESC enhancer starr_02785 Neighboring gene microRNA 1843b Neighboring gene small Cajal body-specific RNA 3A Neighboring gene STARR-seq mESC enhancer starr_02786 Neighboring gene predicted gene, 31256 Neighboring gene STARR-seq mESC enhancer starr_02787 Neighboring gene STARR-seq mESC enhancer starr_02788 Neighboring gene STARR-seq mESC enhancer starr_02789 Neighboring gene STARR-seq mESC enhancer starr_02790 Neighboring gene tenascin R Neighboring gene STARR-seq mESC enhancer starr_02791 Neighboring gene predicted gene, 31348

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. E3 ubiquitin ligase COP1 confers neuroprotection in cerebral ischemia/reperfusion injury via regulation of transcription factor C/EBPβ in microglia. He C, et al. Int J Biol Macromol, 2022 Dec 1. PMID 36191790
    2. A CRISPR Screen Identifies the E3 Ubiquitin Ligase Rfwd2 as a Negative Regulator of Glucose Uptake in Brown Adipocytes. Lynes MD, et al. Genes (Basel), 2023 Sep 26. PMID 37895214, Free PMC Article
    3. Evidence for functional conservation of a mammalian homologue of the light-responsive plant protein COP1. Wang H, et al. Curr Biol, 1999 Jul 1. PMID 10395541
    4. Formation of Arabidopsis Cryptochrome 2 photobodies in mammalian nuclei: application as an optogenetic DNA damage checkpoint switch. Ozkan-Dagliyan I, et al. J Biol Chem, 2013 Aug 9. PMID 23833191, Free PMC Article
    5. In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target. Wang X, et al. Cell, 2021 Oct 14. PMID 34582788, Free PMC Article

    See all (50) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A CRISPR Screen Identifies the E3 Ubiquitin Ligase Rfwd2 as a Negative Regulator of Glucose Uptake in Brown Adipocytes.
      Title: A CRISPR Screen Identifies the E3 Ubiquitin Ligase Rfwd2 as a Negative Regulator of Glucose Uptake in Brown Adipocytes.
    2. E3 ubiquitin ligase COP1 confers neuroprotection in cerebral ischemia/reperfusion injury via regulation of transcription factor C/EBPbeta in microglia.
      Title: E3 ubiquitin ligase COP1 confers neuroprotection in cerebral ischemia/reperfusion injury via regulation of transcription factor C/EBPβ in microglia.
    3. In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target.
      Title: In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target.
    4. Mechanistically, cryptochromes inactivate Cop1 by interacting with Det1, a subunit of the mammalian CRL4(Cop1) complex that is not present in other CRL4s. Through this interaction, the ability of Cop1 to join the CRL4 complex is inhibited; therefore, its substrates accumulate. Thus, the interaction between cryptochromes and Det1 in mammals mirrors the interaction between cryptochromes and Cop1 in planta.
      Title: Cryptochromes-Mediated Inhibition of the CRL4(Cop1)-Complex Assembly Defines an Evolutionary Conserved Signaling Mechanism.
    5. Lipotoxicity led to up-regulation of COP1 at both the gene and protein levels.
      Title: TRB3 stimulates SIRT1 degradation and induces insulin resistance by lipotoxicity via COP1.
    6. Prenatal inactivation of Rfwd2 gene in the lung epithelium led to a striking halt in branching morphogenesis shortly after secondary branch formation.
      Title: E3 ubiquitin ligase RFWD2 controls lung branching through protein-level regulation of ETV transcription factors.
    7. Study shows that post-translational regulation of the transcription factors ETV1, ETV4, and ETV5 by the ubiquitin ligase COP1 (also called RFWD2) in beta cells is critical for insulin secretion. Mice lacking COP1 in beta cells developed diabetes due to insulin granule docking defects that were fully rescued by genetic deletion of Etv1, Etv4, and Etv5.
      Title: β-Cell Insulin Secretion Requires the Ubiquitin Ligase COP1.
    8. These results indicate that COP1 and Trib1 act as an oncoprotein complex functioning upstream of C/EBPalpha, and its ligase activity is crucial for leukemogenesis.
      Title: COP1 targets C/EBPα for degradation and induces acute myeloid leukemia via Trib1.
    9. COP1 physically interacted with PTP1B and suppressed PTP1B phosphatase activity as well as the association of PTP1B with IRbeta.
      Title: Interaction of constitutive photomorphogenesis 1 protein with protein-tyrosine phosphatase 1B suppresses protein-tyrosine phosphatase 1B activity and enhances insulin signaling.
    10. Modulation of fatty acid synthase degradation by concerted action of p38 MAP kinase, E3 ligase COP1, and SH2-tyrosine phosphatase Shp2.
      Title: Modulation of fatty acid synthase degradation by concerted action of p38 MAP kinase, E3 ligase COP1, and SH2-tyrosine phosphatase Shp2.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    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

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin protein ligase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ubiquitin protein ligase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    Process Evidence Code Pubs
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to ionizing radiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to ionizing radiation ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    part_of Cul4A-RING E3 ubiquitin ligase complex IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of Cul4A-RING E3 ubiquitin ligase complex ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in Golgi membrane ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in nuclear speck IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase COP1
    Names
    E3 ubiquitin-protein ligase RFWD2
    RING finger and WD repeat domain protein 2
    RING-type E3 ubiquitin transferase RFWD2
    constitutive photomorphogenesis protein 1 homolog
    constitutive photomorphogenic protein 1
    mCOP1
    ring finger and WD repeat domain 2
    NP_001347807.1
    NP_036061.1
    XP_006496923.1
    XP_030110253.1
    XP_030110256.1
    XP_030110257.1

    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.

    mRNA and Protein(s)

    1. NM_001360878.2 → NP_001347807.1  E3 ubiquitin-protein ligase COP1 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC084287, AC113597
      UniProtKB/TrEMBL
      B2RXW4
      Conserved Domains (4) summary
      sd00039
      Location:471 → 508
      7WD40; WD40 repeat [structural motif]
      cd16504
      Location:134 → 179
      RING-HC_COP1; RING finger, HC subclass, found in constitutive photomorphogenesis protein 1 (COP1) and similar proteins
      cl25539
      Location:238 → 729
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
      cl26688
      Location:138 → 230
      DWNN; DWNN domain

    2. NM_001428831.1 → NP_001415760.1  E3 ubiquitin-protein ligase COP1 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC084287, AC113597

    3. NM_001428832.1 → NP_001415761.1  E3 ubiquitin-protein ligase COP1 isoform 4

      Status: VALIDATED

      Source sequence(s)
      AC084287, AC113597

    4. NM_001428833.1 → NP_001415762.1  E3 ubiquitin-protein ligase COP1 isoform 5

      Status: VALIDATED

      Source sequence(s)
      AC084287, AC113597

    5. NM_011931.5 → NP_036061.1  E3 ubiquitin-protein ligase COP1 isoform 1

      See identical proteins and their annotated locations for NP_036061.1

      Status: VALIDATED

      Source sequence(s)
      AC084287, AC113597
      Consensus CDS
      CCDS35745.1
      UniProtKB/Swiss-Prot
      Q9R1A8
      UniProtKB/TrEMBL
      B2RXW4
      Related
      ENSMUSP00000076160.6, ENSMUST00000076894.11
      Conserved Domains (3) summary
      cd00200
      Location:423 → 729
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
      pfam00097
      Location:138 → 175
      zf-C3HC4; Zinc finger, C3HC4 type (RING finger)
      sd00039
      Location:475 → 512
      7WD40; WD40 repeat [structural motif]

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000067.7 Reference GRCm39 C57BL/6J

      Range
      159059734..159182442
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_030254393.2 → XP_030110253.1  E3 ubiquitin-protein ligase COP1 isoform X1

      Conserved Domains (2) summary
      PLN00181
      Location:3 → 491
      PLN00181; protein SPA1-RELATED; Provisional
      sd00039
      Location:233 → 270
      7WD40; WD40 repeat [structural motif]

    2. XM_030254396.2 → XP_030110256.1  E3 ubiquitin-protein ligase COP1 isoform X2

      Conserved Domains (2) summary
      PLN00181
      Location:56 → 433
      PLN00181; protein SPA1-RELATED; Provisional
      sd00039
      Location:175 → 212
      7WD40; WD40 repeat [structural motif]

    3. XM_006496860.4 → XP_006496923.1  E3 ubiquitin-protein ligase COP1 isoform X1

      Conserved Domains (2) summary
      PLN00181
      Location:3 → 491
      PLN00181; protein SPA1-RELATED; Provisional
      sd00039
      Location:233 → 270
      7WD40; WD40 repeat [structural motif]

    4. XM_030254397.1 → XP_030110257.1  E3 ubiquitin-protein ligase COP1 isoform X2

      Conserved Domains (2) summary
      PLN00181
      Location:56 → 433
      PLN00181; protein SPA1-RELATED; Provisional
      sd00039
      Location:175 → 212
      7WD40; WD40 repeat [structural motif]

    RNA

    1. XR_004942526.1 RNA Sequence

    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9R1A8.2 GenPept UniProtKB/Swiss-Prot:Q9R1A8

    Gene LinkOut

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

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