# CHMP4C curation notes

## 2026-06-02 review

Falcon deep research was started with `just deep-research-falcon human CHMP4C`; the run timed out after 600 seconds with `All providers failed` and did not write a `CHMP4C-deep-research-falcon.md` report. This review is therefore based on the fetched UniProt/GOA records and cached publications.

CHMP4C is a Snf7-family ESCRT-III paralog, but the strongest CHMP4C-specific literature points to abscission checkpoint regulation rather than to CHMP4B-like execution of endosomal cargo sorting, HIV release, and completion of cytokinesis. UniProt summarizes CHMP4C as an ESCRT-III component and explicitly highlights cytokinesis checkpoint control: phosphorylated CHMP4C with ANCHR retains VPS4 at the midbody ring until checkpoint signaling ends [UniProt:Q96CF2 "component of the cytokinesis checkpoint"; UniProt:Q96CF2 "retains abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated"; UniProt:Q96CF2 "Phosphorylated at Ser-210 by AURKB during cytokinesis"].

The key primary paper shows that CHMP4C is the CHMP4 paralog specialized for Aurora B/NoCut abscission checkpoint control. CHMP4C is a human ESCRT-III subunit involved in abscission timing, functions in the Aurora B-dependent abscission checkpoint, engages Borealin/CPC, and inhibits abscission when phosphorylated by Aurora B [PMID:22422861 "charged multivesicular body (MVB) protein 4C (CHMP4C), a human ESCRT-III subunit, is involved in abscission timing"; PMID:22422861 "CHMP4C functioned in the Aurora B-dependent abscission checkpoint"; PMID:22422861 "CHMP4C engaged the chromosomal passenger complex (CPC) via interaction with Borealin"; PMID:22422861 "CHMP4C inhibits abscission upon phosphorylation by Aurora B"]. CHMP4C-depleted cells complete abscission faster, and S210-dependent localization to the Flemming body is required for the checkpoint [PMID:22422861 "depletion of CHMP4C reduced abscission time by approximately 30 minutes"; PMID:22422861 "Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body and acts as a brake upon the late stages of cytokinesis"; PMID:22422861 "CHMP4C depletion circumvents the NoCut abscission checkpoint"].

The same paper is important negative evidence against over-annotating CHMP4C to CHMP4B-like MVB degradation and HIV release. Depletion of CHMP4B prevented MHC-I degradation, whereas CHMP4A or CHMP4C depletion had little effect; depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release, and only CHMP4B inhibited that process; CHMP4A and CHMP4C were dispensable for completion of cytokinesis while CHMP4B was required [PMID:22422861 "depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect"; PMID:22422861 "depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release and only depletion of CHMP4B inhibited this ESCRT-dependent process"; PMID:22422861 "CHMP4A and CHMP4C were dispensable for completion of cytokinesis, whereas CHMP4B was again the sole paralog required"]. Therefore viral budding and broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context, not as CHMP4C core function.

Borealin/CPC and ANCHR papers provide mechanistic support. Borealin interacts directly with Snf7/CHMP4 components and Aurora B phosphorylates CHMP4C in its C-terminal regulatory region; mutation of those sites causes cytokinesis defects, supporting an abscission-timing checkpoint role [PMID:22724069 "Borealin interacts directly with the Snf7 components of ESCRT-III"; PMID:22724069 "Aurora B kinase, phosphorylates one of the three human Snf7 paralogues-CHMP4C-in its C-terminal tail"; PMID:22724069 "Phosphorylation at these sites appears essential for CHMP4C function because their mutation leads to cytokinesis defects"]. ANCHR/ZFYVE19 acts with CHMP4C to retain VPS4 at the midbody ring and delay abscission in an Aurora-B-dependent manner [PMID:24814515 "In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring"; PMID:24814515 "association prevents VPS4 relocalization to the abscission zone"; PMID:24814515 "abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring"].

CHMP4C still has bona fide ESCRT-III context. ALIX binds C-terminal residues of human CHMP4A-C, and CHMP4 proteins are recruited by ALIX in ESCRT pathways [PMID:18511562 "ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex"; PMID:18511562 "Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)"]. The 2022 MIT-domain interactome emphasizes CHMP4C's distinct C-terminal insertion and specialized checkpoint role; CHMP4C peptide competed for AMSH MIT binding but not MITD1 or USP8, unlike other CHMP4 paralogs [PMID:36107470 "CHMP4C performs a unique role in abscission checkpoint regulation"; PMID:36107470 "CHMP4C bound AMSH MIT (Ki 14 uM), but still failed to bind MITD1 or USP8"].

PN/autophagy annotations should be conservative. CHMP4C is included in the PN ESCRT-III autophagophore closure bucket, and ESCRT/MVB function is broadly required for autophagic clearance [PMID:17984323 "Functional multivesicular bodies are required for autophagic clearance"]. However, the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector. Therefore autophagy, autophagosome maturation, autophagosome membrane, amphisome, and lysosomal-membrane annotations are retained as plausible PN-relevant ESCRT-family context but not identified as CHMP4C's core function.

Generic protein binding and homodimerization annotations are over-annotated. CHMP4C's informative molecular role is ESCRT-III regulatory/checkpoint function through ALIX/CPC/ANCHR/VPS4-associated assemblies; generic protein binding does not convey that mechanism. Viral budding annotations are also likely paralog over-annotations for CHMP4C because CHMP4C depletion did not inhibit HIV-1 release in the paralog comparison paper.