Target type: cellularcomponent
A protein complex between the ATPase VCP (p97) and its cofactor p47 (NSFL1C). In human, the protein complex consists of one homotrimer of NSFL1C/p47 per homohexamer of VCP/p97. [GOC:bf, GOC:PARL, PMID:9214505]
The VCP-NSFL1C complex is a protein complex involved in the ubiquitin-proteasome system, a crucial cellular pathway for protein degradation. The complex is composed of two main components:
- **Valosin-containing protein (VCP), also known as p97:** VCP is an ATPase that acts as a molecular motor, using ATP hydrolysis to extract ubiquitinated proteins from cellular compartments. It is a hexameric protein with two ATPase domains and a substrate-binding domain.
- **NSFL1C (N-terminal domain of NSF-like protein 1C), also known as p47:** NSFL1C is an adaptor protein that interacts with VCP and other proteins to regulate the recruitment and delivery of substrates to the complex. It possesses multiple domains, including a ubiquitin-binding domain, a VCP-binding domain, and a domain that interacts with other cofactors.
The VCP-NSFL1C complex operates within various cellular compartments, including the endoplasmic reticulum (ER), the Golgi apparatus, and the nucleus. It plays a key role in several cellular processes, such as:
- **ER-associated protein degradation (ERAD):** The complex removes misfolded or damaged proteins from the ER, preventing their accumulation and ensuring proper cellular function.
- **Membrane trafficking:** VCP-NSFL1C participates in vesicle budding and fusion, facilitating the transport of proteins and lipids within the cell.
- **DNA repair:** The complex is involved in the repair of DNA damage, contributing to the maintenance of genomic integrity.
- **Autophagy:** VCP-NSFL1C participates in the degradation of cellular components through autophagy, a process essential for cellular renewal and survival.
The VCP-NSFL1C complex is highly regulated by various factors, including ubiquitination, phosphorylation, and interaction with other proteins. Dysregulation of this complex is linked to several diseases, including neurodegenerative disorders, cancer, and immune system dysfunction.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Transitional endoplasmic reticulum ATPase | A transitional endoplasmic reticulum ATPase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P55072] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| clotrimazole | conazole antifungal drug; imidazole antifungal drug; imidazoles; monochlorobenzenes | antiinfective agent; environmental contaminant; xenobiotic | |
| Methylenedioxycinnamic acid | hydroxycinnamic acid | ||
| 3,4-methylenedioxy-beta-nitrostyrene | 3,4-methylenedioxy-beta-nitrostyrene: tyrosine kinase inhibitor that prevents platelet glycoprotein IIb/IIIa activation; structure in first source | ||
| 4-(4-(4-chloro-phenyl)thiazol-2-ylamino)phenol | substituted aniline | ||
| ML240 | ML240 : A member of the class of quinazolines that is quinazoline which is substituted at positions 2, 5 and 8 by 2-amino-1H-benzimidazol-1-yl, benzylnitrilo and methoxy groups, respectively. It is a ATP-competetive inhibitor of AAA ATPase p97, also known as valosin-containing protein (VCP). | aromatic amine; aromatic ether; benzimidazoles; primary amino compound; quinazolines; secondary amino compound | antineoplastic agent |
| ganciclovir | 2-aminopurines; oxopurine | antiinfective agent; antiviral drug |