# UFD1 (Q92890) research notes

## Summary
UFD1 (Ubiquitin recognition factor in ER-associated degradation protein 1; also UFD1L, ubiquitin fusion degradation protein 1) is an essential ubiquitin-binding cofactor of the AAA+ ATPase VCP/p97. It forms the obligate UFD1-NPL4 heterodimer, the principal substrate-recruiting adaptor of p97, and with VCP constitutes the VCP-NPL4-UFD1 segregase. UFD1 binds (poly)ubiquitin and, together with NPL4, recognizes ubiquitinated substrates and presents them to p97 for ATP-driven extraction and unfolding, after which they are degraded by the proteasome. The complex is central to endoplasmic-reticulum-associated degradation (ERAD), driving retrotranslocation of misfolded proteins from the ER to the cytosol, and participates in many other p97-dependent processes including the cellular response to misfolded proteins, ribosome-associated quality control, spindle disassembly and nuclear-envelope reformation at the end of mitosis, and Golgi membrane reassembly. UFD1 also contributes to a non-canonical p97 function in innate immunity, acting (with NPLOC4/VCP) as a negative regulator of type I interferon production by binding RIG-I (RIGI) and recruiting RNF125 for its degradation, and it couples the ER stress response to cell-cycle control via interaction with USP13. The gene lies within the 3q29 / DiGeorge (22q11)-associated genomic context and is developmentally expressed. UFD1 localizes to the cytosol, ER and nucleus.

## Core functions (from review)
- **GO:0031593 polyubiquitin modification-dependent protein binding** — Ubiquitin-recognition cofactor of the AAA+ ATPase VCP/p97 that, as part of the obligate UFD1-NPL4 heterodimer, binds (poly)ubiquitinated substrates and presents them to p97 for ATP-driven extraction and unfolding, after which they are degraded by the proteasome.
- **GO:0031593 polyubiquitin modification-dependent protein binding** — Substrate-delivery subunit of the VCP-NPL4-UFD1 segregase essential for ERAD, driving retrotranslocation of misfolded proteins from the ER to the cytosol for proteasomal degradation and supporting the cellular response to misfolded proteins.

## Provenance
Research and verbatim supporting quotes are recorded inline in `UFD1-ai-review.yaml` (per-annotation `supported_by` and `references` findings). This notes file summarizes the completed review; see the YAML for evidence citations.