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

Summary

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, Dec 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

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_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Endonuclease-mediated (2)
Gene trapped (3) 1 citation
Targeted (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MGI:3033238 (e-PCR)
- UniSTS:274185

C87010 (e-PCR)
- UniSTS:167276

RH126982 (e-PCR)
- UniSTS:207237

05.MMHAP25FLB2.seq (e-PCR)
- UniSTS:122804

RH136121 (e-PCR)
- UniSTS:210116

RH142379 (e-PCR)
- UniSTS:231626

Pou5f1 (e-PCR), detects polymorphism
- UniSTS:478966

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

EC 2.3.2.27

NP_036061.1

EC 2.3.2.27

XP_006496923.1

EC 2.3.2.27

XP_030110253.1

EC 2.3.2.27

XP_030110256.1

EC 2.3.2.27

XP_030110257.1

EC 2.3.2.27

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)

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

Status: VALIDATED

Source sequence(s)

AC084287, AC113597

UniProtKB/TrEMBL

B2RXW4
NM_001428832.1 → NP_001415761.1 E3 ubiquitin-protein ligase COP1 isoform 4

Status: VALIDATED

Source sequence(s)

AC084287, AC113597
NM_001428833.1 → NP_001415762.1 E3 ubiquitin-protein ligase COP1 isoform 5

Status: VALIDATED

Source sequence(s)

AC084287, AC113597
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

NC_000067.7 Reference GRCm39 C57BL/6J

Range

159059734..159182442

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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]
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]
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]
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]