Page last updated: 2024-10-24
COP9 signalosome
Definition
Target type: cellularcomponent
A protein complex that catalyzes the deneddylation of proteins, including the cullin component of SCF ubiquitin E3 ligase; deneddylation increases the activity of cullin family ubiquitin ligases. The signalosome is involved in many regulatory process, including some which control development, in many species; also regulates photomorphogenesis in plants; in many species its subunits are highly similar to those of the proteasome. [PMID:11019806, PMID:12186635, PMID:14570571]
The COP9 signalosome (CSN) is a multiprotein complex that plays a crucial role in regulating diverse cellular processes, including protein degradation, signal transduction, and cell cycle progression. It is a highly conserved complex found in eukaryotes and is composed of eight subunits: CSN1 (also known as Nedd8-specific protease 1 or COPS1), CSN2 (COPS2), CSN3 (COPS3), CSN4 (COPS4), CSN5 (COPS5), CSN6 (COPS6), CSN7 (COPS7), and CSN8 (COPS8).
The CSN complex is primarily localized to the nucleus and cytoplasm, where it interacts with various protein substrates and regulatory factors. The core structure of the CSN complex resembles a crown-like shape, with a central platform composed of CSN1, CSN2, and CSN3, which are involved in substrate recognition and binding. This central platform is flanked by two arms, each formed by a pair of subunits: CSN4-CSN5 and CSN6-CSN7. CSN8, the smallest subunit, associates with the CSN1-CSN2-CSN3 platform.
The CSN complex functions as a deubiquitinating enzyme (DUB), specifically targeting the ubiquitin-like protein NEDD8 (Neural Precursor Cell Expressed Developmentally Down-regulated protein 8). NEDD8 conjugation (NEDDylation) to cullin proteins, a family of scaffold proteins involved in ubiquitination, is a crucial step in activating cullin-RING ubiquitin ligases (CRLs). CRLs are multi-subunit E3 ligases responsible for tagging proteins with ubiquitin, leading to their degradation by the proteasome. The CSN complex, through its deNEDDylation activity, regulates the activity of CRLs by removing NEDD8 from cullin proteins, thereby controlling the ubiquitination process and protein degradation.
Beyond its role in protein degradation, the CSN complex is implicated in various other cellular processes. For instance, it influences signal transduction pathways by regulating the activity of signaling molecules, such as NF-κB, a transcription factor involved in inflammation and immune responses. It also participates in cell cycle regulation by controlling the levels of key cell cycle regulators, such as cyclins and cyclin-dependent kinases (CDKs). Additionally, the CSN complex is linked to developmental processes, including plant development and embryogenesis.
The CSN complex represents a highly regulated and intricate molecular machine that plays a central role in maintaining cellular homeostasis by controlling protein degradation, signal transduction, and cell cycle progression. Its diverse functions highlight its essential role in the regulation of cellular processes and its involvement in various cellular events. '
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Proteins (8)
| Protein | Definition | Taxonomy |
|---|---|---|
| 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 | A 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 that is encoded in the genome of cow. [OMA:P08487, PRO:DNx] | Bos taurus (cattle) |
| COP9 signalosome complex subunit 5 | A COP9 signalosome complex subunit 5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92905] | Homo sapiens (human) |
| Growth factor receptor-bound protein 2 | A growth factor receptor-bound protein 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P62993] | Homo sapiens (human) |
| Myosin-9 | A myosin-9 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P35579] | Homo sapiens (human) |
| 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 | A 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P19174] | Homo sapiens (human) |
| Endoplasmic reticulum chaperone BiP | An endoplasmic reticulum chaperone BiP that is encoded in the genome of human. [PRO:DAN] | Homo sapiens (human) |
| Heat shock 70 kDa protein 1A | A heat shock 70 kDa protein 1A that is encoded in the genome of human. [PRO:DAN, UniProtKB:P0DMV8] | Homo sapiens (human) |
| Heat shock protein HSP 90-beta | A heat shock protein HSP 90-beta that is encoded in the genome of human. [PRO:DAN] | Homo sapiens (human) |
Compounds (63)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| adenine | 6-aminopurines; purine nucleobase | Daphnia magna metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite | |
| dichlorophen | Dichlorophen: Nontoxic laxative vermicide effective for taenia infestation. It tends to produce colic and nausea. It is also used as a veterinary fungicide, anthelmintic, and antiprotozoan. (From Merck, 11th ed.) | bridged diphenyl fungicide; diarylmethane | |
| n(6),n(6)-dimethyladenine | N(6),N(6)-dimethyladenine : A tertiary amine that is adenine substituted at N-6 by geminal methyl groups. | tertiary amine | |
| hexachlorophene | hexachlorophene : An organochlorine compound that is diphenylmethane in which each of the phenyl groups is substituted by chlorines at positions 2, 3, and 5, and by a hydroxy group at position 6. An antiseptic that is effective against Gram-positive organisms, it is used in soaps and creams for the treatment of various skin disorders. It is also used in agriculture as an acaricide and fungicide, but is not approved for such use within the European Union. Hexachlorophene: A chlorinated bisphenol antiseptic with a bacteriostatic action against Gram-positive organisms, but much less effective against Gram-negative organisms. It is mainly used in soaps and creams and is an ingredient of various preparations used for skin disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p797) | bridged diphenyl fungicide; polyphenol; trichlorobenzene | acaricide; antibacterial agent; antifungal agrochemical; antiseptic drug |
| triclosan | aromatic ether; dichlorobenzene; monochlorobenzenes; phenols | antibacterial agent; antimalarial; drug allergen; EC 1.3.1.9 [enoyl-[acyl-carrier-protein] reductase (NADH)] inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; fungicide; persistent organic pollutant; xenobiotic | |
| adenosine diphosphate | Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. | adenosine 5'-phosphate; purine ribonucleoside 5'-diphosphate | fundamental metabolite; human metabolite |
| 2,2'-methylenebis(ethyl-6-tert-butylphenol) | |||
| anthranilamide | substituted aniline | ||
| 2,2'-methylenebis(4-methyl-6-tert-butylphenol) | diarylmethane | ||
| ethamivan | etamivan : Phenol substituted at C-2 and C-4 by a methoxy group and an N,N-diethylaminocarbonyl group respectively. A respiratory stimulant drug related to nikethamide, it has now fallen largely into disuse. ethamivan: minor descriptor (65-72); major descriptor (73-86); on-line search BENZAMIDES (66-86); INDEX MEDICUS search BENZAMIDES (65-72); ETHAMIVAN (73-86) | methoxybenzenes; phenols | |
| oxyclozanide | Oxyclozanide: Anthelmintic used in grazing animals for fasciola and cestode infestations. | ||
| phosphotyrosine | O(4)-phospho-L-tyrosine : A non-proteinogenic L-alpha-amino acid that is L-tyrosine phosphorylated at the phenolic hydroxy group. Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis. | L-tyrosine derivative; non-proteinogenic L-alpha-amino acid; O(4)-phosphotyrosine | Escherichia coli metabolite; immunogen |
| silybin | silibinin : A flavonolignan isolated from milk thistle, Silybum marianum, that has been shown to exhibit antioxidant and antineoplastic activities. | aromatic ether; benzodioxine; flavonolignan; polyphenol; secondary alpha-hydroxy ketone | antineoplastic agent; antioxidant; hepatoprotective agent; plant metabolite |
| adenosine | quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit | adenosines; purines D-ribonucleoside | analgesic; anti-arrhythmia drug; fundamental metabolite; human metabolite; vasodilator agent |
| epigallocatechin gallate | (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin. epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis) | flavans; gallate ester; polyphenol | antineoplastic agent; antioxidant; apoptosis inducer; geroprotector; Hsp90 inhibitor; neuroprotective agent; plant metabolite |
| 3-pentadecylphenol | 3-pentadecylphenol: structure in first source | phenols | |
| 2-acetylamino-3-chloro-1,4-naphthoquinone | 2-acetylamino-3-chloro-1,4-naphthoquinone: structure in first source | ||
| 2,2'-bisphenol f | 2,2'-bisphenol F: contact allergen; structure given in first source | diarylmethane | |
| 8-mercaptoquinoline | 8-mercaptoquinoline: structure given in first source | ||
| 8-aminoadenosine | |||
| 5-benzyloxytryptophan | |||
| isopentaquine | |||
| Zearalanone | macrolide; resorcinols | ||
| 6-n-tridecylsalicylic acid | 6-n-tridecylsalicylic acid: structure given in first source | hydroxybenzoic acid | |
| (-)-gallocatechin gallate | (-)-gallocatechin gallate : A gallate ester obtained by formal condensation of the carboxy group of gallic acid with the (3R)-hydroxy group of (-)-gallocatechin. A natural product found in found in green tea. | catechin; gallate ester; polyphenol | antineoplastic agent; EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor; human xenobiotic metabolite; plant metabolite |
| 8-(2-chloro-3,4,5-trimethoxybenzyl)-2-fluoro-9-pent-4-yn-1-yl-9H-purin-6-amine | 8-(2-chloro-3,4,5-trimethoxybenzyl)-2-fluoro-9-pent-4-yn-1-yl-9H-purin-6-amine : A member of the class of 6-aminopurines that is 2-fluoroadenine carrying additional 2-chloro-3,4,5-trimethoxybenzyl and pent-4-yn-1-yl substituents at positions 8 and 9 respectively. | 6-aminopurines; acetylenic compound; methoxybenzenes; monochlorobenzenes; organofluorine compound | antineoplastic agent; Hsp90 inhibitor |
| dactinomycin | Dactinomycin: A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015) | actinomycin | mutagen |
| 1,3,6-trimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dione | pyrimidotriazine | ||
| cct018159 | CCT-018159 : A member of the class of pyrazoles that is 1H-pyrazole carrying 1,4-benzodioxane-6-yl and 5-ethyl-2,4-dihydroxyphenyl substituents at positions 4 and 5 respectively. CCT018159: structure in first source | benzodioxine; pyrazoles; resorcinols | antineoplastic agent; apoptosis inducer; Hsp90 inhibitor |
| 1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dione | pyrimidotriazine | ||
| blister | blebbistatin : A pyrroloquinoline that is 1,2,3,3a-tetrahydro-H-pyrrolo[2,3-b]quinolin-4-one substituted by a hydroxy group at position 3a, a methyl group at position 6 and a phenyl group at position 1. It acts as an inhibitor of ATPase activity of non-muscle myosin II. blebbistatin: structure in first source | cyclic ketone; pyrroloquinoline; tertiary alcohol; tertiary alpha-hydroxy ketone | inhibitor |
| ver-49009 | 5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)pyrazole-3-carboxamide : An aromatic amide obtained by formal condensation of the carboxy group of 5-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)pyrazole-3-carboxylic acid with the amino group of ethylamine. VER-49009: inhibits heat shock protein 90 molecular chaperone; structure in first source | aromatic amide; monochlorobenzenes; monomethoxybenzene; pyrazoles; resorcinols | Hsp90 inhibitor |
| amentoflavone | biflavonoid; hydroxyflavone; ring assembly | angiogenesis inhibitor; antiviral agent; cathepsin B inhibitor; P450 inhibitor; plant metabolite | |
| myricetin | 7-hydroxyflavonol; hexahydroxyflavone | antineoplastic agent; antioxidant; cyclooxygenase 1 inhibitor; food component; geroprotector; hypoglycemic agent; plant metabolite | |
| bilobol | bilobol: structure given in first source; RN given refers to (Z)-isomer; RN for cpd without isomeric designation not avail 6/90 | 5-alkenylresorcinol | |
| ginkgolic acid | hydroxybenzoic acid | ||
| geldanamycin | 1,4-benzoquinones; ansamycin; carbamate ester; organic heterobicyclic compound | antimicrobial agent; antineoplastic agent; antiviral agent; cysteine protease inhibitor; Hsp90 inhibitor | |
| 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin | 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: structure in first source alvespimycin : A 19-membered macrocyle that is geldanamycin in which the methoxy group attached to the benzoquinone moiety has been replaced by a 2-(N,N-dimethylamino)ethylamino group. | 1,4-benzoquinones; ansamycin; carbamate ester; secondary amino compound; tertiary amino compound | Hsp90 inhibitor |
| 7-hydroxycoumarin-4-acetic acid | 7-hydroxycoumarin-4-acetic acid: pH-indicator dye; structure in first source | ||
| derrubone | derrubone: an inhibitor of the Hsp90 protein folding machinery from Derris robusta; structure in first source | isoflavanones | |
| monorden | monorden: inhibits HSP90 Heat-Shock Proteins, DNA topoisomerase VI and human Topoisomerase II | cyclic ketone; enone; epoxide; macrolide antibiotic; monochlorobenzenes; phenols | antifungal agent; metabolite; tyrosine kinase inhibitor |
| tanespimycin | CP 127374: analog of herbimycin A | 1,4-benzoquinones; ansamycin; carbamate ester; organic heterobicyclic compound; secondary amino compound | antineoplastic agent; apoptosis inducer; Hsp90 inhibitor |
| vildagliptin | amino acid amide | ||
| 9h-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-n-(1-methylethyl)- | 9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-: an epichaperome (purine-scaffold) inhibitor; structure in first source | ||
| nvp-dpp728 | |||
| cycloproparadicicol | cycloproparadicicol: structure in first source | ||
| gambogic acid | gambogic acid: RN given refers to (1R-(1alpha,1(Z),3abeta,5alpha,11beta,14aS*))-isomer | pyranoxanthones | metabolite |
| ipi 493 | 17-aminogeldanamycin: structure in first source | ||
| pochonin d | pochonin D: secondary metabolite of Pochonia chlamydosporia; structure in first source | ||
| snx-7081 | SNX-7081: Anti-Inflammatory Agent; structure in first source | ||
| at 13387 | (2,4-dihydroxy-5-isopropylphenyl)-(5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl)methanone: structure in first source onalespib : A member of the class of isoindoles that is isoindole in which the amino group has been acylated by a 2,4-dihydroxy-5-isopropylbenzoyl group and in which position 5 of the isoidole moiety has been substituted by a (4-methylpiperazin-1-yl)methyl group. A second-generation Hsp90 inhibitor. | benzamides; isoindoles; N-alkylpiperazine; resorcinols; tertiary carboxamide | antineoplastic agent; Hsp90 inhibitor |
| cnf 2024 | 2-aminopurines; aromatic ether; organochlorine compound; pyridines | antineoplastic agent; Hsp90 inhibitor | |
| snx 2112 | SNX 2112: an orally available small molecule Hsp90 inhibitor; structure in first source | ||
| ver 155008 | VER 155008: structure in first source | purine nucleoside | |
| nvp-bep800 | |||
| debio 0932 | CUDC 305: an Hsp90 inhibitor with antineoplastic activity; structure in first source | ||
| novobiocin | novobiocin : A coumarin-derived antibiotic obtained from Streptomyces niveus. Novobiocin: An antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189) | carbamate ester; ether; hexoside; hydroxycoumarin; monocarboxylic acid amide; monosaccharide derivative; phenols | antibacterial agent; antimicrobial agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; Escherichia coli metabolite; hepatoprotective agent |
| tas-116 | |||
| ver-246608 | VER-246608: inhibits pyruvate dehydrogenase kinase; structure in first source | ||
| ver-50589 | VER-50589: inhibits heat shock protein 90 molecular chaperone; structure in first source | ||
| ver 52296 | luminespib : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-(2,4-dihydroxy-5-isopropylphenyl)-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxylic acid with the amino group of ethylamine. | aromatic amide; isoxazoles; monocarboxylic acid amide; morpholines; resorcinols | angiogenesis inhibitor; antineoplastic agent; Hsp90 inhibitor |
| sta 9090 | ring assembly; triazoles | ||
| nms-e973 | NMS-E973: structure in first source |