Cul4B-RING E3 ubiquitin ligase complex
Definition
Target type: cellularcomponent
A ubiquitin ligase complex in which a cullin from the Cul4B subfamily and a RING domain protein form the catalytic core; substrate specificity is conferred by unknown subunits. [PMID:15571813, PMID:15688063]
The Cul4B-RING E3 ubiquitin ligase complex is a multi-protein assembly that plays a crucial role in protein ubiquitination, a process critical for diverse cellular functions. The complex consists of several key components, each contributing to its overall function.
1. **Cullin 4B (Cul4B):** This protein serves as the scaffold for the complex. Its N-terminal domain interacts with the RING domain of RBX1, while its C-terminal domain binds to the adaptor protein DDB1.
2. **DDB1:** This adaptor protein acts as a bridge, connecting Cul4B to substrate recognition modules called WD40 repeat proteins. These modules are specific for different target proteins, thus allowing Cul4B to regulate a wide range of cellular processes.
3. **RBX1 (RING-box protein 1):** This protein possesses a RING domain, which is essential for the complex's E3 ligase activity. The RING domain interacts with an E2 ubiquitin-conjugating enzyme, facilitating the transfer of ubiquitin from the E2 to the target protein.
4. **WD40 repeat proteins:** These proteins provide specificity to the complex by binding to specific target proteins. The WD40 repeats form a beta-propeller structure, allowing for the interaction with diverse substrates. Some examples of WD40 repeat proteins associated with Cul4B include:
* **DDB2:** This protein acts as a DNA damage sensor and is involved in nucleotide excision repair.
* **VPRBP:** This protein participates in viral restriction and is linked to immune responses.
* **CDT2:** This protein is crucial for DNA replication and cell cycle control.
5. **E2 ubiquitin-conjugating enzyme:** This enzyme plays a critical role in transferring ubiquitin from itself to the target protein. The E2 enzyme interacts with the RING domain of RBX1, facilitating this transfer step.
The Cul4B-RING E3 ubiquitin ligase complex assembles into a functional unit through intricate protein-protein interactions. The complex uses its E3 ligase activity to attach ubiquitin chains to target proteins, ultimately leading to their degradation or functional modification. This process is essential for regulating a wide range of cellular processes, including DNA damage repair, cell cycle control, immune responses, and viral restriction.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Methylosome protein 50 | A methylosome protein WDR77 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9BQA1] | Homo sapiens (human) |
| DNA damage-binding protein 1 | A DNA damage-binding protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16531] | Homo sapiens (human) |
Compounds (10)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| thalidomide | 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group. thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide. Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action. | phthalimides; piperidones | |
| s-adenosylmethionine | acylcarnitine: structure in first source S-adenosyl-L-methioninate : A sulfonium betaine that is a conjugate base of S-adenosyl-L-methionine obtained by the deprotonation of the carboxy group. | sulfonium betaine | human metabolite |
| pomalidomide | 3-aminophthalimidoglutarimide: structure in first source | aromatic amine; dicarboximide; isoindoles; piperidones | angiogenesis inhibitor; antineoplastic agent; immunomodulator |
| lenalidomide | aromatic amine; dicarboximide; isoindoles; piperidones | angiogenesis inhibitor; antineoplastic agent; immunomodulator | |
| s-adenosylhomocysteine | S-adenosyl-L-homocysteine : An organic sulfide that is the S-adenosyl derivative of L-homocysteine. S-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions. | adenosines; amino acid zwitterion; homocysteine derivative; homocysteines; organic sulfide | cofactor; EC 2.1.1.72 [site-specific DNA-methyltransferase (adenine-specific)] inhibitor; EC 2.1.1.79 (cyclopropane-fatty-acyl-phospholipid synthase) inhibitor; epitope; fundamental metabolite |
| 5'-methylthioadenosine | 5'-methylthioadenosine: structure 5'-S-methyl-5'-thioadenosine : Adenosine with the hydroxy group at C-5' substituted with a methylthio (methylsulfanyl) group. | thioadenosine | algal metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| jq1 compound | carboxylic ester; organochlorine compound; tert-butyl ester; thienotriazolodiazepine | angiogenesis inhibitor; anti-inflammatory agent; antineoplastic agent; apoptosis inducer; bromodomain-containing protein 4 inhibitor; cardioprotective agent; ferroptosis inducer | |
| epz004777 | N-glycosyl compound | ||
| gsk3235025 | GSK3235025: an inhibitor of protein arginine methyltransferase-5 (PRMT5); structure in first source | ||
| MZ1 | organic molecular entity |