COP9 signalosome complex subunit 6 [Caenorhabditis elegans]
Protein Classification
MPN domain-containing protein( domain architecture ID 46114)
MPN domain-containing protein contains the signature JAB1/MPN/Mov34 metalloenzyme (JAMM) motif, which is involved in zinc ion coordination; similar to components of the COP9 signalosome (CSN) complex that acts as a regulator of the ubiquitin conjugation pathway
List of domain hits
| Name | Accession | Description | Interval | E-value | |||||
| MPN super family | cl13996 | Mpr1p, Pad1p N-terminal (MPN) domains; MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) ... |
13-269 | 3.68e-49 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains; MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) domains are found in the N-terminal termini of proteins with a variety of functions; they are components of the proteasome regulatory subunits, the signalosome (CSN), eukaryotic translation initiation factor 3 (eIF3) complexes, and regulators of transcription factors. These domains are isopeptidases that release ubiquitin from ubiquitinated proteins (thus having deubiquitinating (DUB) activity) that are tagged for degradation. Catalytically active MPN domains contain a metalloprotease signature known as the JAB1/MPN/Mov34 metalloenzyme (JAMM) motif. For example, Rpn11 (also known as POH1 or PSMD14), a subunit of the 19S proteasome lid is involved in the ATP-dependent degradation of ubiquitinated proteins, contains the conserved JAMM motif involved in zinc ion coordination. Poh1 is a regulator of c-Jun, an important regulator of cell proliferation, differentiation, survival and death. JAB1 is a component of the COP9 signalosome (CSN), a regulatory particle of the ubiquitin (Ub)/26S proteasome system occurring in all eukaryotic cells; it cleaves the ubiquitin-like protein NEDD8 from the cullin subunit of the SCF (Skp1, Cullins, F-box proteins) family of E3 ubiquitin ligases. AMSH (associated molecule with the SH3 domain of STAM, also known as STAMBP), a member of JAMM/MPN+ deubiquitinases (DUBs), specifically cleaves Lys 63-linked polyubiquitin (poly-Ub) chains, thus facilitating the recycling and subsequent trafficking of receptors to the cell surface. Similarly, BRCC36, part of the nuclear complex that includes BRCA1 protein and is targeted to DNA damage foci after irradiation, specifically disassembles K63-linked polyUb. BRCC36 is aberrantly expressed in sporadic breast tumors, indicative of a potential role in the pathogenesis of the disease. Some variants of the JAB1/MPN domains lack key residues in their JAMM motif and are unable to coordinate a metal ion. Comparisons of key catalytic and metal binding residues explain why the MPN-containing proteins Mov34/PSMD7, Rpn8, CSN6, Prp8p, and the translation initiation factor 3 subunits f (p47) and h (p40) do not show catalytic isopeptidase activity. It has been proposed that the MPN domain in these proteins has a primarily structural function. The actual alignment was detected with superfamily member cd08063: Pssm-ID: 472685 [Multi-domain] Cd Length: 288 Bit Score: 168.97 E-value: 3.68e-49
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| Name | Accession | Description | Interval | E-value | |||||
| MPN_CSN6 | cd08063 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 ... |
13-269 | 3.68e-49 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 signalosome complex subunit 6; CSN6 (COP9 signalosome subunit 6; COP9 subunit 6; MOV34 homolog, 34 kD) is one of the eight subunits of COP9 signalosome, a highly conserved protein complex with diverse functions, including several important intracellular pathways such as the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. CSN6 is an MPN-domain protein that directly interacts with the MPN+-domain subunit CSN5. It is cleaved during apoptosis by activated caspases. CSN6 processing occurs in CSN/CRL (cullin-RING Ub ligase) complexes and is followed by the cleavage of Rbx1, the direct interaction partner of CSN6. CSN6 cleavage enhances CSN-mediated deneddylating activity (i.e. cleavage of ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells. The cleavage of Rbx1 and increased deneddylation of cullins inactivate CRLs and presumably stabilize pro-apoptotic factors for final apoptotic steps. While CSN6 shows a typical MPN metalloprotease fold, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity. Pssm-ID: 163694 [Multi-domain] Cd Length: 288 Bit Score: 168.97 E-value: 3.68e-49
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| MitMem_reg | pfam13012 | Maintenance of mitochondrial structure and function; This is C-terminal to the Mov24 region of ... |
178-245 | 1.27e-12 | |||||
Maintenance of mitochondrial structure and function; This is C-terminal to the Mov24 region of the yeast proteasomal subunit Rpn11 and seems likely to regulate the mitochondrial fission and tubulation processes, ie the outer mitochondrial membrane proteins. This function appears to be unrelated to the proteasome activity of the N-terminal region. Pssm-ID: 463772 [Multi-domain] Cd Length: 72 Bit Score: 62.90 E-value: 1.27e-12
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| PLN03246 | PLN03246 | 26S proteasome regulatory subunit; Provisional |
12-242 | 7.80e-09 | |||||
26S proteasome regulatory subunit; Provisional Pssm-ID: 215645 [Multi-domain] Cd Length: 303 Bit Score: 56.67 E-value: 7.80e-09
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| JAB_MPN | smart00232 | JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ... |
13-158 | 7.17e-05 | |||||
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal subunits. Domain at Mpr1p and Pad1p N-termini. Domain of unknown function. Pssm-ID: 214573 Cd Length: 135 Bit Score: 42.36 E-value: 7.17e-05
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| Name | Accession | Description | Interval | E-value | |||||
| MPN_CSN6 | cd08063 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 ... |
13-269 | 3.68e-49 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 signalosome complex subunit 6; CSN6 (COP9 signalosome subunit 6; COP9 subunit 6; MOV34 homolog, 34 kD) is one of the eight subunits of COP9 signalosome, a highly conserved protein complex with diverse functions, including several important intracellular pathways such as the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. CSN6 is an MPN-domain protein that directly interacts with the MPN+-domain subunit CSN5. It is cleaved during apoptosis by activated caspases. CSN6 processing occurs in CSN/CRL (cullin-RING Ub ligase) complexes and is followed by the cleavage of Rbx1, the direct interaction partner of CSN6. CSN6 cleavage enhances CSN-mediated deneddylating activity (i.e. cleavage of ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells. The cleavage of Rbx1 and increased deneddylation of cullins inactivate CRLs and presumably stabilize pro-apoptotic factors for final apoptotic steps. While CSN6 shows a typical MPN metalloprotease fold, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity. Pssm-ID: 163694 [Multi-domain] Cd Length: 288 Bit Score: 168.97 E-value: 3.68e-49
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| MPN_euk_non_mb | cd08057 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity (non ... |
14-183 | 2.34e-42 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity (non metal-binding); eukaryotic; This family contains MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) domains variants lacking key residues in the JAB1/MPN/Mov34 metalloenzyme (JAMM) motif and are unable to coordinate a metal ion. Comparisons of key catalytic and metal binding residues explain why the MPN-containing proteins Rpn7/PSMD7, Rpn8/PSMD8, CSN6, Prp8p, and the translation initiation factor 3 subunits f and h do not show catalytic isopeptidase activity. It has been proposed that the MPN domain in these proteins has a primarily structural function. Rpn7 is known to be critical for the integrity of the 26S proteasome complex by establishing a correct lid structure. It is necessary for the incorporation/anchoring of Rpn3 and Rpn12 to the lid and essential for viability and normal mitosis. CSN6 is a highly conserved protein complex with diverse functions, including several important intracellular pathways such as the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. It cleaves ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells. EIF3f s a potent inhibitor of HIV-1 replication as well as an important negative regulator of cell growth and proliferation. EIF3h regulates cell growth and viability, and that over-expression of the gene may provide growth advantage to prostate, breast, and liver cancer cells. Pssm-ID: 163688 [Multi-domain] Cd Length: 157 Bit Score: 146.43 E-value: 2.34e-42
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| MitMem_reg | pfam13012 | Maintenance of mitochondrial structure and function; This is C-terminal to the Mov24 region of ... |
178-245 | 1.27e-12 | |||||
Maintenance of mitochondrial structure and function; This is C-terminal to the Mov24 region of the yeast proteasomal subunit Rpn11 and seems likely to regulate the mitochondrial fission and tubulation processes, ie the outer mitochondrial membrane proteins. This function appears to be unrelated to the proteasome activity of the N-terminal region. Pssm-ID: 463772 [Multi-domain] Cd Length: 72 Bit Score: 62.90 E-value: 1.27e-12
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| MPN_eIF3f | cd08064 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF3f; ... |
14-241 | 4.55e-11 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF3f; Eukaryotic translation initiation factor 3 (eIF3) subunit F (eIF3F; EIF3S5; eIF3-p47; eukaryotic translation initiation factor 3, subunit 5 epsilon, 47kDa; Mov34/MPN/PAD-1 family protein) is an evolutionarily non-conserved subunit of the functional core that comprises eIF3a, eIF3b, eIF3c, eIF3e, eIF3f, and eIF3h, and contains the MPN domain. However, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity. It has been shown that eIF3f mRNA expression is significantly decreased in many human tumors including pancreatic cancer and melanoma. EIF3f is a potent inhibitor of HIV-1 replication; it mediates restriction of HIV-1 expression through several factors including the serine/arginine-rich (SR) protein 9G8, and cyclin-dependent kinase 11 (CDK11). EIF3f phosphorylation by CDK11 is important in regulating its function in translation and apoptosis. It enhances its association with the core eIF3 subunits during apoptosis, suggesting that eIF3f may inhibit translation by increasing the binding to the eIF3 complex during apoptosis. Thus, eIF3f may be an important negative regulator of cell growth and proliferation. Pssm-ID: 163695 [Multi-domain] Cd Length: 265 Bit Score: 62.99 E-value: 4.55e-11
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| JAB | pfam01398 | JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome ... |
13-101 | 3.58e-09 | |||||
JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors. This family is also known as the MPN domain and PAD-1-like domain, JABP1 domain or JAMM domain. These are metalloenzymes that function as the ubiquitin isopeptidase/ deubiquitinase in the ubiquitin-based signalling and protein turnover pathways in eukaryotes. Versions of the domain in prokaryotic cognates of the ubiquitin-modification pathway are shown to have a similar role, and the archael protein from Haloferax volcanii is found to cleave ubiquitin-like small archaeal modifier proteins (SAMP1/2) from protein conjugates. Pssm-ID: 396120 Cd Length: 117 Bit Score: 54.27 E-value: 3.58e-09
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| MPN_RPN7_8 | cd08062 | Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in 19S ... |
13-242 | 5.73e-09 | |||||
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in 19S proteasomal subunits Rpn7 and Rpn8; This family includes lid subunits of the 26 S proteasome regulatory particles, Rpn7 (PSMD7; proteasome 26S non-ATPase subunit 7; p44), and Rpn8 (PSMD8; proteasome 26S non-ATPase subunit 8; p40; Mov34). Rpn7 is known to be critical for the integrity of the 26 S proteasome complex by establishing a correct lid structure. It is necessary for the incorporation/anchoring of Rpn3 and Rpn12 to the lid and essential for viability and normal mitosis. Rpn7 and Rpn8 are ATP-independent components of the 19S regulator subunit, and contain the MPN structural motif on its N-terminal region. However, while they show a typical MPN metalloprotease fold, they lack the canonical JAMM motif, and therefore do not show catalytic isopeptidase activity. It is suggested that Rpn7 function is primarily structural. Pssm-ID: 163693 [Multi-domain] Cd Length: 280 Bit Score: 56.82 E-value: 5.73e-09
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| PLN03246 | PLN03246 | 26S proteasome regulatory subunit; Provisional |
12-242 | 7.80e-09 | |||||
26S proteasome regulatory subunit; Provisional Pssm-ID: 215645 [Multi-domain] Cd Length: 303 Bit Score: 56.67 E-value: 7.80e-09
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| JAB_MPN | smart00232 | JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ... |
13-158 | 7.17e-05 | |||||
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal subunits. Domain at Mpr1p and Pad1p N-termini. Domain of unknown function. Pssm-ID: 214573 Cd Length: 135 Bit Score: 42.36 E-value: 7.17e-05
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