Affinage

VCF2

Protein VCF2 · UniProt Q5XKR9

Length
115 aa
Mass
13.1 kDa
Annotated
2026-06-11
2 papers in source corpus 1 papers cited in narrative 1 extracted findings
Cross-family judge faithfulness: 3/3 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VCF2 (FAM104B) is a nuclear cofactor of the AAA+ ATPase p97/VCP that couples p97 to its nuclear functions by directly binding p97 through a novel alpha-helical motif (PMID:37713320). VCF2 associates with the canonical p97-UFD1-NPL4 and p97-UBXN2B complexes in cells and localizes to the nucleus, where it promotes nuclear import of p97 (PMID:37713320). Consistent with this role, loss of VCF2 reduces nuclear p97 levels and produces slow growth and hypersensitivity to p97 inhibition (PMID:37713320). Beyond (PMID:37713320), no further mechanistic detail has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 2023 High

    Established that VCF2/FAM104B is a bona fide p97/VCP cofactor that binds p97 directly via a defined motif and governs the nuclear pool of p97, answering how p97 is delivered to and functions in the nucleus.

    Evidence Pulldown/Co-IP with mutagenesis of the alpha-helical binding motif, reciprocal Co-IP for complex association, imaging/fractionation for localization, and knockdown/knockout with growth and drug-sensitivity readouts in cells

    PMID:37713320

    Open questions at the time
    • Structural basis of the alpha-helical motif engaging p97 not resolved at atomic resolution
    • Mechanism by which VCF2 drives nuclear import of p97 (import machinery, cargo handoff) not defined
    • Substrates or nuclear processes downstream of VCF2-dependent p97 import not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether VCF2 selects or processes specific p97 substrates in the nucleus, and how its activity is regulated, remains unknown.
  • No nuclear substrate of the VCF2-p97 axis characterized
  • Regulation of VCF2 expression or activity unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 1 R-HSA-9609507 Protein localization 1
Partners
NPLOC4UBXN2BUFD1VCP
Complex memberships
p97-UBXN2Bp97-UFD1-NPL4

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 VCF2 (FAM104B) directly binds p97/VCP via a novel alpha-helical motif, associates with p97-UFD1-NPL4 and p97-UBXN2B complexes in cells, localizes to the nucleus, and promotes nuclear import of p97; loss of VCF2 results in reduced nuclear p97 levels, slow growth, and hypersensitivity to p97 inhibition. Direct binding established by pulldown/Co-IP with mutagenesis of the alpha-helical motif; complex association by Co-immunoprecipitation in cells; subcellular localization by imaging/fractionation; loss-of-function (knockdown/knockout) with growth and drug-sensitivity phenotypic readouts eLife High 37713320

Source papers

Stage 0 corpus · 2 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Pulmonary embolus after vena cava filter placement. The American surgeon 20 10190360
2023 The FAM104 proteins VCF1/2 promote the nuclear localization of p97/VCP. eLife 6 37713320

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