Vcp (rat, UniProt P46462) - manual literature synthesis

No deep-research provider was available for this review. This file was written by
hand from the cached publications in publications/ and the UniProt record
(Vcp-uniprot.txt). Every claim carries an inline citation with a verbatim quote.

Identity and architecture

• Rat Vcp (p97, transitional endoplasmic reticulum ATPase, TER ATPase) is the rat
  ortholog of yeast Cdc48 and human VCP. It was first isolated from rat liver
  transitional ER as a hexameric ATPase PMID:7806566.
• Domain organisation: an N domain plus two AAA ATPase domains, D1 and D2
  PMID:18332143. The
  record carries two Pfam AAA domains (PF00004), CDC48_N (PF02359), CDC48_2 (PF02933)
  and the NCBIfam TIGR01243 CDC48 family signature (Vcp-uniprot.txt).

ATPase and nucleotide binding (rat protein, direct evidence)

• Recombinant rat p97 was used to measure nucleotide binding to D1 and D2
  PMID:18332143.
• ATPgammaS binds both domains; ADP binds D1 more tightly PMID:18332143.
• D2 is the main site of ATP hydrolysis PMID:18332143.
• Cooperativity within the hexamer PMID:18332143.

Cofactor complexes (rat liver cytosol, direct evidence)

• p97 forms two mutually exclusive major complexes PMID:10811609.
• p47 complex: one p47 trimer per p97 hexamer PMID:9214505. Cryo-EM structures of the p97-p47 complex in two nucleotide states
  PMID:16601695.
• Ufd1-Npl4 complex PMID:10811609; cryo-EM PMID:22232657.
• A p47 F253S point mutant fails to bind p97 PMID:20691684.

Membrane fusion and Golgi reassembly (p97-p47)

• p47 is the cofactor for p97-mediated regrowth of Golgi cisternae PMID:9214505.
• Only p97/p47, not p97/Ufd1/Npl4, drives reassembly [PMID:10811609 "Only a combination
  of p97 and p47 could promote reassembly."; "Neither p97/Ufd1/Npl4 nor p97/Ufd1
  promoted cisternal regrowth from mitotic Golgi fragments."].
• Earlier work implicated the TER ATPase in transition-vesicle formation from rat liver
  tER PMID:7806566.

ERAD and retrotranslocation (p97-Ufd1-Npl4)

• p97 is required to export ER proteins to the cytosol PMID:11740563.
• Dual recognition and ATP-driven extraction PMID:12847084; p97 itself binds polyubiquitin
  PMID:12847084; domain roles PMID:12847084.
• Endogenous ERAD substrate in rat cells: IP3 receptors PMID:16103111. The effect was specific: bulk UPP degradation was unaffected
  PMID:16103111.
• Membrane recruitment via Derlin-1/VIMP (human cells) PMID:16186510.
• Cytosolic localisation in rat beta-cells, interacting with ERAD machinery (SDF2L1
  study, PMID:23444373; abstract only).

Other ubiquitin-dependent extraction roles (orthologs; By similarity in UniProt)

• Autophagosome maturation (human cells) PMID:20104022.
• Endolysosomal sorting of ubiquitylated caveolin-1 with UBXD1 PMID:21822278.
• Mitophagy via UBXD1 recruitment PMID:30120381.
• Stress granule clearance PMID:29804830.
• DNA damage: extraction of L3MBTL1 PMID:22120668 and trapped PARP1
  PMID:35013556.
• Lipid droplets via UBXD8 PMID:23297223.

Neuronal / synaptic

• Rat hippocampal neurons: VCP with neurofibromin controls dendritic spine density
  PMID:22105171 (abstract only).

Indirect phenotypes (caution)

• Patient fibroblasts with VCP mutations show mitochondrial uncoupling and low ATP
  PMID:23498975. These are downstream phenotypes, not activities of VCP.
• Poliovirus replication requires VCP PMID:22379090: host-dependency evidence.