COP9 constitutive photomorphogenic homolog subunit 5 (Arabidopsis), also known as COPS5 or Csn5, is a gene conserved from humans to Saccharomyces cerevisiae. [5]
COP9 constitutive photomorphogenic homolog subunit 5 (Arabidopsis), also known as COPS5 or Csn5, is a gene conserved from humans to Saccharomyces cerevisiae. [5]
The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein is reported to be involved in the degradation of cyclin-dependent kinase inhibitor CDKN1B/p27Kip1. It is also known to be a coactivator that increases the specificity of JUN/AP1 transcription factors. [5]
COP9 constitutive photomorphogenic homolog subunit 5 has been shown to interact with Macrophage migration inhibitory factor, [6] [7] GFER, [8] BCL3, [9] Ubiquitin carboxy-terminal hydrolase L1, [10] S100A7 [11] and C-jun. [12]
Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, where it acts as a scaffold to recruit proteins involved in DNA replication, DNA repair, chromatin remodeling and epigenetics.
S-phase kinase-associated protein 2 is an enzyme that in humans is encoded by the SKP2 gene.
Myb-related protein B is a protein that in humans is encoded by the MYBL2 gene.
NEDD8 is a protein that in humans is encoded by the NEDD8 gene. This ubiquitin-like (UBL) protein becomes covalently conjugated to a limited number of cellular proteins, in a process called NEDDylation similar to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity to ubiquitin. The primary known substrates of NEDD8 modification are the cullin subunits of cullin-based E3 ubiquitin ligases, which are active only when NEDDylated. Their NEDDylation is critical for the recruitment of E2 to the ligase complex, thus facilitating ubiquitin conjugation. NEDD8 modification has therefore been implicated in cell cycle progression and cytoskeletal regulation.
COP9 signalosome complex subunit 6 is a protein that in humans is encoded by the COPS6 gene.
Mediator of RNA polymerase II transcription subunit 1 also known as DRIP205 or Trap220 is a subunit of the Mediator complex and is a protein that in humans is encoded by the MED1 gene. MED1 functions as a nuclear receptor coactivator.
DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene.
COP9 signalosome complex subunit 2 is a protein that in humans is encoded by the COPS2 gene. It encodes a subunit of the COP9 signalosome.
CDC34 is a gene that in humans encodes the protein Ubiquitin-conjugating enzyme E2 R1. This protein is a member of the ubiquitin-conjugating enzyme family, which catalyzes the covalent attachment of ubiquitin to other proteins.
Cullin-2 is a protein that in humans is encoded by the CUL2 gene.
Cyclin-dependent kinases regulatory subunit 1 is a protein that in humans is encoded by the CKS1B gene.
Cullin-4B is a protein that in humans is encoded by the CUL4B gene which is located on the X chromosome. CUL4B has high sequence similarity with CUL4A, with which it shares certain E3 ubiquitin ligase functions. CUL4B is largely expressed in the nucleus and regulates several key functions including: cell cycle progression, chromatin remodeling and neurological and placental development in mice. In humans, CUL4B has been implicated in X-linked intellectual disability and is frequently mutated in pancreatic adenocarcinomas and a small percentage of various lung cancers. Viruses such as HIV can also co-opt CUL4B-based complexes to promote viral pathogenesis. CUL4B complexes containing Cereblon are also targeted by the teratogenic drug thalidomide.
COP9 signalosome complex subunit 3 is a protein that in humans is encoded by the COPS3 gene. It encodes a subunit of the COP9 signalosome.
COP9 signalosome complex subunit 4 is a protein that in humans is encoded by the COPS4 gene.
COP9 signalosome complex subunit 8 is a protein that in humans is encoded by the COPS8 gene.
COP9 signalosome complex subunit 1 is a protein that in humans is encoded by the GPS1 gene.
COP9 signalosome complex subunit 7a is a protein that in humans is encoded by the COPS7A gene.
COP9 signalosome complex subunit 7b is a protein that in humans is encoded by the COPS7B gene.
Myeloid leukemia factor 1 is a protein that in humans is encoded by the MLF1 gene.
COP9 signalosome (CSN) is a protein complex with isopeptidase activity. It catalyses the hydrolysis of NEDD8 protein from the cullin subunit of Cullin-RING ubiquitin ligases (CRL). Therefore, it is responsible for CRL deneddylation – at the same time, it is able to bind denedyllated cullin-RING complex and retain them in deactivated form. COP9 signalosome thus serves as a sole deactivator of CRLs. The complex was originally identified in plants, and subsequently found in all eukaryotic organisms including human. Human COP9 signalosome consists of 8 subunits - CSN1, CSN2, CSN3, CSN4, CSN5, CSN6, CSN7, CSN8. All are essential for full function of the complex and mutation in some of them is lethal in mice.