proteasome core complex, alpha-subunit complex
Definition
Target type: cellularcomponent
The proteasome core subcomplex that constitutes the two outer rings of the proteasome core complex. An example of this component is found in Mus musculus. [GOC:jl, GOC:mtg_sensu, GOC:rb, PMID:10854779]
The proteasome core complex, alpha-subunit complex, is a 14-subunit ring structure that forms the outer chamber of the 26S proteasome. This ring is responsible for recognizing and binding to ubiquitinated proteins destined for degradation. Each alpha-subunit is approximately 25 kDa in size and contains a unique N-terminal domain that projects into the central cavity of the ring. These domains are essential for the regulatory functions of the complex, including substrate selection, gate opening, and preventing the uncontrolled degradation of cellular proteins. The alpha-subunit complex also plays a role in maintaining the structural integrity of the proteasome, ensuring its proper assembly and stability. Its specific functions include:
* **Substrate recognition**: The N-terminal domains of the alpha-subunits interact with ubiquitin chains attached to target proteins, facilitating their recognition and binding.
* **Gate control**: The alpha-subunit ring forms a gate that controls the entry of proteins into the proteolytic chamber.
* **Structural stability**: The alpha-subunit complex provides a rigid scaffold that supports the assembly and stability of the proteasome.
The alpha-subunit complex is highly conserved across different organisms and is essential for maintaining cellular homeostasis by controlling protein turnover. Mutations in the alpha-subunits can lead to various cellular dysfunctions and disease states.'
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Proteins (8)
| Protein | Definition | Taxonomy |
|---|---|---|
| Proteasome subunit alpha-type 8 | A proteasome subunit alpha-type 8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8TAA3] | Homo sapiens (human) |
| Proteasome subunit alpha type-6 | A proteasome subunit alpha type-6 that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Proteasome subunit alpha type-5 | A proteasome subunit alpha type-5 that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Proteasome subunit alpha type-4 | A proteasome subunit alpha type-4 that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Proteasome subunit alpha type-3 | A proteasome subunit alpha type-3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P25788] | Homo sapiens (human) |
| Proteasome subunit alpha type-2 | A proteasome subunit alpha type-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P25787] | Homo sapiens (human) |
| Proteasome subunit alpha type-1 | A proteasome subunit alpha type-1 that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Proteasome subunit alpha type-7 | A proteasome subunit alpha type-7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O14818] | Homo sapiens (human) |
Compounds (19)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| chlorpromazine | chlorpromazine : A substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety. Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. | organochlorine compound; phenothiazines; tertiary amine | anticoronaviral agent; antiemetic; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; phenothiazine antipsychotic drug |
| clomipramine | clomipramine : A dibenzoazepine that is 10,11-dihydro-5H-dibenzo[b,f]azepine which is substituted by chlorine at position 3 and in which the hydrogen attached to the nitrogen is replaced by a 3-(dimethylamino)propyl group. One of the more sedating tricyclic antidepressants, it is used as the hydrochloride salt for the treatment of depression as well as obsessive-compulsive disorder and phobias. Clomipramine: A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine. | dibenzoazepine | anticoronaviral agent; antidepressant; EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor; serotonergic antagonist; serotonergic drug; serotonin uptake inhibitor |
| methixene | methixene: RN given refers to parent cpd; structure | piperidines; thioxanthenes | antiparkinson drug; histamine antagonist; muscarinic antagonist |
| thioridazine | thioridazine : A phenothiazine derivative having a methylsulfanyl subsitituent at the 2-position and a (1-methylpiperidin-2-yl)ethyl] group at the N-10 position. Thioridazine: A phenothiazine antipsychotic used in the management of PHYCOSES, including SCHIZOPHRENIA. | phenothiazines; piperidines | alpha-adrenergic antagonist; dopaminergic antagonist; EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; first generation antipsychotic; H1-receptor antagonist; serotonergic antagonist |
| triflupromazine | triflupromazine : A member of the class of phenothiazines that is 10H-phenothiazine having a trifluoromethyl subsitituent at the 2-position and a 3-(dimethylamino)propyl group at the N-10 position. Triflupromazine: A phenothiazine used as an antipsychotic agent and as an antiemetic. | organofluorine compound; phenothiazines; tertiary amine | anticoronaviral agent; antiemetic; dopaminergic antagonist; first generation antipsychotic |
| bortezomib | amino acid amide; L-phenylalanine derivative; pyrazines | antineoplastic agent; antiprotozoal drug; protease inhibitor; proteasome inhibitor | |
| sdz 283-910 | SDZ 283-910: structure in first source | ||
| benzyloxycarbonylleucyl-leucyl-leucine aldehyde | benzyloxycarbonylleucyl-leucyl-leucine aldehyde: proteasome inhibitor N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal : A tripeptide that is L-leucyl-L-leucyl-L-leucine in which the C-terminal carboxy group has been reduced to the corresponding aldehyde and the N-terminal amino group is protected as its benzyloxycarbonyl derivative. | amino aldehyde; carbamate ester; tripeptide | proteasome inhibitor |
| benzyloxycarbonyl-phe-ala-fluormethylketone | cathepsin B inhibitor : A cysteine protease inhibitor which inhibits cathepsin B (EC 3.4.22.1). | ||
| am 404 | anilide | ||
| lactacystin | lactam; S-substituted L-cysteine | ||
| clasto-lactacystin beta-lactone | clasto-lactacystin beta-lactone: active metabolite of lactacystin; inhibits 20 S proteasome; structure in first source | ||
| marizomib | marizomib: a proteasome inhibitor from a marine bacterium Salinospora; structure in first source | beta-lactone; gamma-lactam; organic heterobicyclic compound; organochlorine compound; salinosporamide | antineoplastic agent; proteasome inhibitor |
| carfilzomib | epoxide; morpholines; tetrapeptide | antineoplastic agent; proteasome inhibitor | |
| tyropeptin a | tyropeptin A: proteasome inhibitors produced by Kitasatospora sp. MK993-dF2; structure in first source | dipeptide | |
| pr-957 | |||
| belactosin a | belactosin A: isolated from Streptomyces; structure in first source | ||
| oprozomib | ONX 0912: antineoplastic; an orally active proteasome inhibitor; structure in first source | ||
| ixazomib | ixazomib : A glycine derivative that is the amide obtained by formal condensation of the carboxy group of N-(2,5-dichlorobenzoyl)glycine with the amino group of [(1R)-1-amino-3-methylbutyl]boronic acid. The active metabolite of ixazomib citrate, it is used in combination therapy for treatment of multiple myeloma. ixazomib: a proteasome inhibitor with antineoplastic activity; MLN2238 is the biologically active form of MLN9708; structure in first source | benzamides; boronic acids; dichlorobenzene; glycine derivative | antineoplastic agent; apoptosis inducer; drug metabolite; orphan drug; proteasome inhibitor |