Existing Annotations Review

Core Functions

CHMP1B binds MIT domains of VPS4 ATPases and spastin via its C-terminal MIM motif, with particularly high affinity for spastin (12 μM KD) enabling recruitment of spastin to midbodies for cytokinetic abscission and VPS4 for ESCRT-III disassembly. This bifunctional binding enables context-dependent protein partnerships for diverse membrane remodeling processes including MVB formation, endosomal recycling, and cytokinesis.

Molecular Function:

MIT domain binding

Supporting Evidence:

file:human/CHMP1B/CHMP1B-uniprot.txt
Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with SPAST (via MIT domain); the interaction is direct
file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
The spastin MIT domain recognizes CHMP1B with a dissociation constant of approximately 12 μM, approximately 2.75-fold higher affinity than VPS4 MIT domain binding. This dual-function capacity of the CHMP1B MIM for selective binding to both VPS4 and spastin represents a remarkable example of molecular adaptation

CHMP1B self-associates to form helical filaments on membranes, either as homopolymers or as 1:1 copolymers with IST1. These polymers mediate membrane constriction and scission with dual topology specificity - reverse-topology for MVB ILV formation and normal-topology for endosomal recycling tubule scission.

Molecular Function:

identical protein binding

Supporting Evidence:

file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
CHMP1B initially polymerizes into flexible single-stranded filaments that wrap around target membranes to induce moderate curvature, followed by subsequent IST1 assembly onto CHMP1B to progressively constrict the membrane. The two strands interweave extensively, with CHMP1B helix α4 binding to multiple segments of the IST1 N-terminal domain helix α1, creating a tightly interlocked structure

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:14505570

The protein network of HIV budding

PMID:14519844

Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins

PMID:16174732

Structure and ESCRT-III protein interactions of the MIT domain of human VPS4A

PMID:16505166

Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1

PMID:16554368

The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor

PMID:16730941

A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.

PMID:17711858

The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation

PMID:17928862

ESCRT-III recognition by VPS4 ATPases

PMID:17984323

Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease

PMID:18385515

Novel interactions of ESCRT-III with LIP5 and VPS4 and their implications for ESCRT-III disassembly

PMID:18997780

Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes

PMID:19129479

Biochemical analyses of human IST1 and its function in cytokinesis

PMID:19129480

Essential role of hIST1 in cytokinesis

PMID:19234443

Membrane scission by the ESCRT-III complex

PMID:19302785

Ab initio protein modelling reveals novel human MIT domains

PMID:19525971

Structural basis for ESCRT-III protein autoinhibition

PMID:20458337

MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis

PMID:20588296

Membrane budding and scission by the ESCRT machinery: it's all in the neck.

PMID:20616062

Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance

PMID:21543490

Mechanism of inhibition of retrovirus release from cells by interferon-induced gene ISG15

PMID:21827950

Structural basis for ESCRT-III CHMP3 recruitment of AMSH

PMID:21988832

Toward an understanding of the protein interaction network of the human liver

PMID:23015756

MITD1 is recruited to midbodies by ESCRT-III and participates in cytokinesis

PMID:23045692

ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes

PMID:23105106

Interactions of the human LIP5 regulatory protein with endosomal sorting complexes required for transport

PMID:23533145

In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine

PMID:24482116

ESCRT machinery is required for plasma membrane repair

PMID:24878737

Structure of cellular ESCRT-III spirals and their relationship to HIV budding

PMID:25416956

A proteome-scale map of the human interactome network

PMID:25556234

New host factors important for respiratory syncytial virus (RSV) replication revealed by a novel microfluidics screen for interactors of matrix (M) protein.

PMID:26040712

Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing

PMID:26040713

ESCRT-III controls nuclear envelope reformation

PMID:26634441

Structure and membrane remodeling activity of ESCRT-III helical polymers

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations

PMID:32296183

A reference map of the human binary protein interactome

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome

PMID:36107470

Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics

file:human/CHMP1B/CHMP1B-deep-research-perplexity.md

Deep research on CHMP1B function and mechanisms

file:human/CHMP1B/CHMP1B-uniprot.txt

UniProt entry for CHMP1B

Deep Research

Falcon

(CHMP1B-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 18 citations 2025-12-14T17:17:20.155556

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research plan and verification
- Identity verification: CHMP1B (UniProt Q7LBR1) corresponds to the human charged multivesicular body protein 1b, an ESCRT-III/SNF7-family subunit with Snf7-type domains. Contemporary reviews place CHMP1B among ESCRT-III proteins that assemble into membrane-associated polymers to remodel and sever membranes, consistent with the SNF7 family/domain assignment and human organism context (Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294) (park2024escrtiiiaversatile pages 13-14, park2024escrtiiiaversatile pages 4-5). No conflicting gene symbol usage was identified in the retrieved literature.

Comprehensive research report on human CHMP1B (Q7LBR1)

1) Key concepts and definitions
- Core identity: CHMP1B is an ESCRT-III subunit (SNF7 family) that polymerizes on membranes to drive negative-curvature membrane remodeling and fission in diverse contexts, including endosomal intraluminal vesicle (ILV) formation, cytokinetic abscission, nuclear envelope surveillance/repair, plasma membrane repair, and the budding of enveloped viruses. ESCRT-III dynamics are powered by the AAA ATPase VPS4, which disassembles ESCRT-III polymers to complete membrane fission cycles (Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294; Frontiers in Microbiology, 2023-10; https://doi.org/10.3389/fmicb.2023.1261651) (park2024escrtiiiaversatile pages 4-5, wang2023insightsintothe pages 3-5).
- Specific partners and roles: CHMP1B directly interacts with the microtubule-severing ATPase spastin to coordinate microtubule severing at the intercellular bridge during cytokinetic abscission. It also engages with the ESCRT-III protein IST1 to form copolymers that coat positively curved endosomal tubules and contribute to tubulation/constriction; these activities are regulated by VPS4 (Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294; PNAS, 2024-04; https://doi.org/10.1073/pnas.2317680121; Frontiers in Microbiology, 2023-10; https://doi.org/10.3389/fmicb.2023.1261651) (park2024escrtiiiaversatile pages 7-8, knyazeva2024achemicalinhibitor pages 1-2, wang2023insightsintothe pages 3-5).

2) Recent developments and latest research (priority to 2023–2024)
- Chemical tool targeting CHMP1B–IST1: A natural product-like small molecule, Tantalosin, was discovered that selectively disrupts the IST1–CHMP1B interaction and impairs IST1–CHMP1B copolymer formation. In human cells, Tantalosin stalls transferrin receptor recycling at sorting endosomes and triggers noncanonical LC3 lipidation (CASM) on these stalled endosomes, illuminating a causal role for IST1–CHMP1B in endosomal recycling-homeostasis and in coupling ESCRT arrest to noncanonical autophagy machinery recruitment (PNAS, 2024-04; https://doi.org/10.1073/pnas.2317680121) (knyazeva2024achemicalinhibitor pages 1-2).
- Cytokinetic abscission mechanics: A 2024 study refined how actin and ESCRT-III cooperate at the abscission site. CHMP1B intensity correlates with local microtubule severing, consistent with CHMP1B-dependent recruitment of spastin and the separation of microtubule cut from subsequent membrane scission. This work supports a two-step model: actin-dependent microtubule severing followed by ESCRT-III-driven membrane scission, with CHMP1B part of the ESCRT-III cone near the midbody (Nature Communications, 2024-03; https://doi.org/10.1038/s41467-024-46062-9) (park2024escrtiiiaversatile pages 7-8).
- Genome integrity and nuclear envelope: A 2024 review synthesizes evidence that ESCRT-III, including CHMP1B, contributes to nuclear envelope repair/resealing and abscission checkpoint control, thereby preserving genome integrity. It highlights ESCRT-III recruitment at the nuclear membrane and midbody, with VPS4-mediated turnover critical for proper remodeling (Cells, 2024-08; https://doi.org/10.3390/cells13151307) (torre2024preservinggenomeintegrity pages 13-14).
- Updated ESCRT-III perspectives: A 2024 review consolidates mechanistic advances on ESCRT-III assembly/disassembly, polymer architecture, and roles across endolysosomal trafficking, viral budding, and membrane repair; it specifically notes CHMP1B’s contribution to polymer tension and membrane bending and its interactions in cytokinesis (Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294) (park2024escrtiiiaversatile pages 4-5, park2024escrtiiiaversatile pages 7-8).

3) Current applications and real-world implementations
- Endosomal recycling and cargo trafficking: Chemical perturbation of IST1–CHMP1B with Tantalosin impairs transferrin receptor recycling, demonstrating a practical handle to modulate ESCRT-III–dependent endosomal remodeling and to induce noncanonical LC3 lipidation at arrested endosomes. This provides an experimental platform to dissect ESCRT–autophagy crosstalk (PNAS, 2024-04; https://doi.org/10.1073/pnas.2317680121) (knyazeva2024achemicalinhibitor pages 1-2).
- Cytokinesis and cell division control: CHMP1B participates in forming the ESCRT-III cone near the midbody, where it cooperates with spastin to sever microtubules prior to membrane fission; ESCRT-III filaments of approximately 17 nm diameter assemble at constriction zones. Depletion of CHMP1B impairs abscission in cell models, underlining its functional requirement for division completion (Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294; Nature Communications, 2024-03; https://doi.org/10.1038/s41467-024-46062-9) (park2024escrtiiiaversatile pages 7-8, park2024escrtiiiaversatile pages 4-5).
- Viral budding: ESCRT-III components, including CHMP1B, are recruited by enveloped viruses to sites of budding to accomplish membrane neck constriction and fission; retroviruses are a canonical example. This knowledge is used to interpret viral assembly pathways and identify host-dependency factors (Frontiers in Microbiology, 2023-10; https://doi.org/10.3389/fmicb.2023.1261651) (wang2023insightsintothe pages 3-5).

4) Expert opinions and analyses from authoritative sources
- Consensus from 2024 reviews: ESCRT-III serves as a universal, ATP-driven membrane scission machine across compartments; CHMP1B is one of the subunits integrated into context-specific polymers. Reviews emphasize the choreography of assembly (e.g., CHMP4 nucleation followed by incorporation of subunits such as CHMP1B) and Vps4-mediated turnover as critical for function, with CHMP1B’s specific roles in tensioning polymers and recruiting spastin at the midbody highlighted (Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294; Cells, 2024-08; https://doi.org/10.3390/cells13151307) (park2024escrtiiiaversatile pages 4-5, torre2024preservinggenomeintegrity pages 13-14, park2024escrtiiiaversatile pages 7-8).
- ESCRT in genome integrity and disease: ESCRT-III activity at the nuclear envelope and the abscission checkpoint protects genome integrity; perturbations of ESCRT-III components are linked to pathologies including cancer and neurodegeneration. The literature places CHMP1B within these protective pathways, particularly at the midbody and nuclear envelope (Cells, 2024-08; https://doi.org/10.3390/cells13151307) (torre2024preservinggenomeintegrity pages 13-14).

5) Relevant statistics and quantitative data
- ESCRT-III filament geometry at abscission: ESCRT-III assembles into filaments with approximate 17 nm diameter at constriction zones within intercellular bridges, consistent with the physical dimensions required for microtubule severing and membrane scission coordination (Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294) (park2024escrtiiiaversatile pages 7-8).
- Functional readouts of CHMP1B–IST1 inhibition: Pharmacological disruption with Tantalosin yields measurable phenotypes—accumulation of transferrin in sorting endosomes and induction of noncanonical LC3 lipidation on these stalled carriers—providing quantitative cell biological endpoints for CHMP1B-dependent endosomal recycling (PNAS, 2024-04; https://doi.org/10.1073/pnas.2317680121) (knyazeva2024achemicalinhibitor pages 1-2).

Mechanistic synthesis: molecular functions, localization, and pathways
- Molecular role and partners: CHMP1B is a polymerizing ESCRT-III subunit that integrates into context-specific assemblies. It interacts with IST1 to form copolymers on positively curved endosomal tubules, promoting tubulation, constriction, and membrane thinning; VPS4 engagement is required for polymer turnover and productive fission. At the midbody, CHMP1B interacts with spastin via MIT-interactions to couple microtubule severing to subsequent ESCRT-III-driven membrane scission (PNAS, 2024-04; https://doi.org/10.1073/pnas.2317680121; Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294; Nature Communications, 2024-03; https://doi.org/10.1038/s41467-024-46062-9) (knyazeva2024achemicalinhibitor pages 1-2, park2024escrtiiiaversatile pages 4-5, park2024escrtiiiaversatile pages 7-8).
- Cellular localization: CHMP1B localizes dynamically to endosomal membranes (notably recycling/sorting endosomes where IST1–CHMP1B act), to the intercellular bridge/midbody during cytokinesis, and to the nuclear membrane in late anaphase/repair situations, consistent with ESCRT-III’s broad deployment (Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294; Cells, 2024-08; https://doi.org/10.3390/cells13151307) (park2024escrtiiiaversatile pages 4-5, torre2024preservinggenomeintegrity pages 13-14, park2024escrtiiiaversatile pages 7-8).
- Pathways and processes:
• Endosomal sorting/recycling: IST1–CHMP1B copolymers facilitate tubule formation and scission in endosomal recycling; chemical disruption causes cargo (transferrin) accumulation and activates noncanonical LC3 lipidation at stalled endosomes (PNAS, 2024-04; https://doi.org/10.1073/pnas.2317680121) (knyazeva2024achemicalinhibitor pages 1-2).
• Cytokinetic abscission: CHMP1B is required for abscission, functioning within the ESCRT-III cone to recruit spastin and coordinate sequential microtubule severing and membrane fission. Depletion blocks abscission and ESCRT-III filaments at abscission zones are ~17 nm in diameter (Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294; Nature Communications, 2024-03; https://doi.org/10.1038/s41467-024-46062-9) (park2024escrtiiiaversatile pages 7-8, park2024escrtiiiaversatile pages 4-5).
• Nuclear envelope repair/reassembly and genome integrity: ESCRT-III, including CHMP1B, is recruited to nuclear membranes during anaphase/telophase and in nuclear envelope quality control, contributing to sealing and checkpoint functions that safeguard genome integrity (Cells, 2024-08; https://doi.org/10.3390/cells13151307) (torre2024preservinggenomeintegrity pages 13-14).
• Autophagy-related processes: When ESCRT function is pharmacologically impeded at endosomes, noncanonical LC3 lipidation (CASM) is induced on stalled endosomes, linking ESCRT-III arrest to ATG8 conjugation machinery; this highlights ESCRT-III’s interface with noncanonical autophagy pathways (PNAS, 2024-04; https://doi.org/10.1073/pnas.2317680121) (knyazeva2024achemicalinhibitor pages 1-2).
• Viral budding: Enveloped viruses recruit ESCRT machinery, including CHMP subunits such as CHMP1B, to effect membrane neck scission and release; this is a conserved host-dependency exploited during budding (Frontiers in Microbiology, 2023-10; https://doi.org/10.3389/fmicb.2023.1261651) (wang2023insightsintothe pages 3-5).

Disease links and biomedical relevance
- Neurodegeneration and cell division: CHMP1B’s interaction with spastin directly ties the protein to a pathway in which mutations in spastin cause hereditary spastic paraplegia; more broadly, ESCRT-III pathway defects are implicated in neurodegeneration and tumorigenesis through failures in abscission checkpoints and nuclear envelope integrity (Cells, 2024-08; https://doi.org/10.3390/cells13151307; Frontiers in Microbiology, 2023-10; https://doi.org/10.3389/fmicb.2023.1261651) (torre2024preservinggenomeintegrity pages 13-14, wang2023insightsintothe pages 3-5).

Tools and resources
- Small-molecule probe: Tantalosin, a selective inhibitor of the IST1–CHMP1B interaction, enables acute perturbation of CHMP1B-dependent endosomal remodeling and assays of endosome–autophagy crosstalk in human cells (PNAS, 2024-04; https://doi.org/10.1073/pnas.2317680121) (knyazeva2024achemicalinhibitor pages 1-2).

Limitations and outlook
- While the cited 2024–2023 studies refine CHMP1B’s roles and provide a first-in-class inhibitor for IST1–CHMP1B, high-resolution CHMP1B-specific structural dynamics within cellular polymers and quantitative kinetics of VPS4-coupled turnover in human cells remain areas for further work. Nevertheless, convergent reviews and primary studies support CHMP1B as an integral ESCRT-III effector in endosomal recycling, cytokinetic abscission, nuclear envelope maintenance, and virus budding (Animal Cells and Systems, 2024-07; https://doi.org/10.1080/19768354.2024.2380294; Cells, 2024-08; https://doi.org/10.3390/cells13151307; Frontiers in Microbiology, 2023-10; https://doi.org/10.3389/fmicb.2023.1261651) (park2024escrtiiiaversatile pages 4-5, torre2024preservinggenomeintegrity pages 13-14, wang2023insightsintothe pages 3-5).

References

(park2024escrtiiiaversatile pages 13-14): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 11 citations and is from a peer-reviewed journal.
(park2024escrtiiiaversatile pages 4-5): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 11 citations and is from a peer-reviewed journal.
(wang2023insightsintothe pages 3-5): Chunxuan Wang, Yu Chen, Shunlin Hu, and Xiufan Liu. Insights into the function of escrt and its role in enveloped virus infection. Frontiers in Microbiology, Oct 2023. URL: https://doi.org/10.3389/fmicb.2023.1261651, doi:10.3389/fmicb.2023.1261651. This article has 29 citations and is from a poor quality or predatory journal.
(park2024escrtiiiaversatile pages 7-8): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 11 citations and is from a peer-reviewed journal.
(knyazeva2024achemicalinhibitor pages 1-2): Anastasia Knyazeva, Shuang Li, Dale P. Corkery, Kasturika Shankar, Laura K. Herzog, Xuepei Zhang, Birendra Singh, Georg Niggemeyer, David Grill, Jonathan D. Gilthorpe, Massimiliano Gaetani, Lars-Anders Carlson, Herbert Waldmann, and Yao-Wen Wu. A chemical inhibitor of ist1-chmp1b interaction impairs endosomal recycling and induces noncanonical lc3 lipidation. Proceedings of the National Academy of Sciences of the United States of America, Apr 2024. URL: https://doi.org/10.1073/pnas.2317680121, doi:10.1073/pnas.2317680121. This article has 15 citations and is from a highest quality peer-reviewed journal.
(torre2024preservinggenomeintegrity pages 13-14): Mattia La Torre, Romina Burla, and Isabella Saggio. Preserving genome integrity: unveiling the roles of escrt machinery. Cells, 13:1307, Aug 2024. URL: https://doi.org/10.3390/cells13151307, doi:10.3390/cells13151307. This article has 10 citations and is from a poor quality or predatory journal.

Citations

knyazeva2024achemicalinhibitor pages 1-2
park2024escrtiiiaversatile pages 7-8
torre2024preservinggenomeintegrity pages 13-14
wang2023insightsintothe pages 3-5
park2024escrtiiiaversatile pages 13-14
park2024escrtiiiaversatile pages 4-5
https://doi.org/10.1080/19768354.2024.2380294
https://doi.org/10.1080/19768354.2024.2380294;
https://doi.org/10.3389/fmicb.2023.1261651
https://doi.org/10.1073/pnas.2317680121;
https://doi.org/10.1073/pnas.2317680121
https://doi.org/10.1038/s41467-024-46062-9
https://doi.org/10.3390/cells13151307
https://doi.org/10.3390/cells13151307;
https://doi.org/10.1080/19768354.2024.2380294,
https://doi.org/10.3389/fmicb.2023.1261651,
https://doi.org/10.1073/pnas.2317680121,
https://doi.org/10.3390/cells13151307,

Perplexity

(CHMP1B-deep-research-perplexity.md)

CHMP1B: Structural Organization, Membrane Remodeling Functions, and Cellular Roles in Protein Sorting and Trafficking Perplexity sonar-deep-research 42 citations 2025-11-23T19:26:04.780813

CHMP1B: Structural Organization, Membrane Remodeling Functions, and Cellular Roles in Protein Sorting and Trafficking

Executive Summary

CHMP1B (Charged Multivesicular Body Protein 1B) is a member of the ESCRT-III (Endosomal Sorting Complex Required for Transport III) protein family that serves as a critical component of the cellular machinery governing membrane remodeling and protein sorting throughout multiple subcellular compartments[2][7]. This protein belongs to the SNF7 family and functions as a peripherally associated component of ESCRT-III complexes involved in multivesicular body (MVB) formation, intraluminal vesicle (ILV) biogenesis, and cargo protein sorting[2][10]. Rather than functioning in isolation, CHMP1B operates through dynamic interactions with partner proteins, most notably IST1, to orchestrate distinct membrane deformation processes with opposing topologies. Recent structural and biochemical studies have revealed that CHMP1B undergoes substantial conformational changes from a closed, cytoplasmic autoinhibited state to open polymerized filaments that coat and sculpt cellular membranes[35][36]. The protein exhibits regulated ubiquitination via the USP8/UBPY deubiquitinase, a mechanism that controls its activity at endosomal membranes in response to growth factor stimulation[14][26][35]. Beyond its canonical roles in MVB biogenesis, CHMP1B participates in cytokinetic abscission, HIV-1 virion release, and endosomal recycling pathways, thereby linking membrane topology remodeling to fundamental cellular processes. Mutations in CHMP1B-related pathways have been identified in pontocerebellar hypoplasia type 8, establishing direct connections between ESCRT-III dysfunction and human neurodevelopmental disease[31][34].

Protein Structure and ESCRT-III Complex Organization

Structural Architecture and Domain Organization

CHMP1B is a 199-amino acid protein that shares significant structural homology with other ESCRT-III family members while maintaining distinct functional properties[2][7]. The protein comprises a highly conserved core domain composed of four central alpha helices arranged in a characteristic hairpin-like arrangement that defines the SNF7 protein family[2][5]. The core structural organization includes helices α1 and α2, which form a compact hairpin motif at the N-terminal region, connected through helical elements α3 and α4 to additional C-terminal helical structures[20][32]. This core domain architecture establishes the fundamental organizational principle shared across ESCRT-III proteins, though the specific arrangement and conformational dynamics of these helical elements in CHMP1B confer its unique functional properties[33].

A crucial distinguishing feature of CHMP1B is its C-terminal tail region, which contains the MIT-interacting motif (MIM) that enables high-affinity interactions with MIT domain-containing proteins such as VPS4 ATPases and the microtubule-severing protein spastin[21][58]. This MIM region demonstrates bifunctional capacity, capable of binding to the MIT domains of both VPS4 and spastin through distinct binding interfaces despite utilizing the same conserved leucine residues[21]. The structural basis for this dual functionality reveals that the spastin MIT domain recognizes the CHMP1B MIM with approximately twelve-fold higher affinity than does the VPS4A MIT domain, suggesting specialized recruitment mechanisms for distinct cellular processes[21][58].

The protein exists in a highly dynamic conformational equilibrium between distinct states. In the cytoplasm, CHMP1B adopts a closed, autoinhibitory conformation wherein the C-terminal helical element folds back against the core domain structure, effectively masking protein-protein interaction surfaces and preventing premature polymerization[32][35][48]. This autoinhibited state maintains the protein in a monomeric configuration through intramolecular interactions that stabilize the closed conformation. Upon membrane recruitment and activation, CHMP1B undergoes dramatic conformational rearrangement, transitioning to an extended open state wherein the C-terminal regions extend away from the core domain, exposing previously buried interaction surfaces[20][35][48]. This activation process requires approximately half of the monomeric protein structure to reorganize, including melding of helices α2 and α3 into an extended helical structure and reorientation of helix α4[56]. The energetic barrier to this conformational transition is a key control point for ESCRT-III function, and recent evidence indicates that various upstream factors and binding partners work in concert to facilitate this activation transition[35][48].

ESCRT-III Complex Context and Hierarchical Assembly

CHMP1B functions as one component within the larger ESCRT-III complex, which is itself one of five sequential ESCRT complexes (ESCRT-0 through ESCRT-III plus VPS4) that orchestrate endosomal cargo sorting and membrane scission[2][14][19][26]. The ESCRT-III complex represents the catalytic core of the ESCRT pathway, directly mediating membrane deformation and fission reactions through the assembly of protein polymers that encircle and constrain membranes[12][24]. The sequential recruitment of these complexes involves initial recognition of ubiquitinated cargo by ESCRT-0 and ESCRT-I complexes, followed by ESCRT-II-mediated clustering and initial membrane bending, which in turn recruits ESCRT-III subunits to sites of active membrane remodeling[2][14][26][38].

Within the ESCRT-III complex, CHMP1B belongs to the CHMP1 subfamily, which includes the related protein CHMP1A and exhibits distinct functional properties compared to other ESCRT-III members such as the CHMP2, CHMP3, and CHMP4 families[8][24][32]. Notably, HIV-1 budding studies revealed that depletion of CHMP2 or CHMP4 family members produces dramatically greater defects (95-166 fold reductions in viral titers) than depletion of CHMP1 proteins (only 2-8 fold reductions), indicating that CHMP1 proteins have more specialized or context-dependent functions[8]. Despite this functional specialization, CHMP1B participates in diverse membrane remodeling processes through distinct molecular mechanisms that depend on its interaction partners and the specific membrane topology involved[9][24].

Molecular Mechanisms in MVB Formation and Membrane Remodeling

Classical Role in MVB Biogenesis and Intraluminal Vesicle Formation

The primary established function of CHMP1B derives from its participation in multivesicular body (MVB) formation, a critical process in which cargo-containing membrane invaginations at the limiting membrane of late endosomal compartments undergo scission to generate intraluminal vesicles (ILVs)[2][14][19][26]. ILVs are small membrane-enclosed vesicles contained within the lumen of MVBs that eventually fuse with lysosomes, enabling proteolytic degradation of sequestered cargo proteins[2][14]. This process represents a major cellular mechanism for downregulation of activated cell surface receptors, particularly receptor tyrosine kinases, and constitutes a critical regulatory node for signal transduction termination[14][26][38].

The formation of ILVs requires extensive membrane remodeling: the plasma membrane of the endosome must undergo inward invagination to generate a bud-like protrusion, the narrow neck of this invaginating membrane must be severely constricted, and ultimately the membrane neck must undergo scission to release the ILV into the endosomal lumen[9][12][24][33]. CHMP1B participates in these steps by assembling into helical polymer structures that encircle invaginating membrane regions. The ESCRT-III filaments composed of CHMP1B and related proteins generate mechanical forces that facilitate membrane deformation and reduce the energetic barrier to membrane fission[9][24][33][36].

The involvement of CHMP1B in this process is particularly important for trafficking of ubiquitinated cargo destined for lysosomal degradation. Studies in plant model systems demonstrated that double mutant plants lacking both CHMP1A and CHMP1B fail to properly sort transmembrane proteins such as auxin carriers (PIN1, PIN2) and auxin receptor AUX1 into ILVs, resulting in their retention within the limiting membrane of MVBs rather than sequestration within ILVs[29]. These mutant MVBs contained significantly fewer ILVs compared to control cells, indicating that CHMP1 proteins are required for efficient intraluminal vesicle formation[29]. The consequence of this sorting defect is altered auxin signaling and disrupted developmental patterning, underscoring the physiological significance of proper MVB cargo sorting[29].

Positive Versus Negative Membrane Curvature Specificity

A remarkable discovery emerging from structural studies has revealed that CHMP1B exhibits distinct membrane curvature specificity compared to other ESCRT-III proteins, with profound implications for understanding its cellular functions[9][24][56]. Most ESCRT-III proteins, exemplified by CHMP4A, assemble into filaments that stabilize negatively curved (or reverse-topology) membranes, wherein the membrane bends away from the cytoplasm into the cytoplasmic lumen of forming vesicles[9][24][43][56]. However, CHMP1B, particularly when functioning in partnership with IST1, assembles into filaments that encircle and stabilize positively curved membranes, wherein the membrane bends toward the cytoplasm[9][12][24][43][56].

This functional dichotomy has profound structural explanations revealed by electron cryomicroscopy analyses. When CHMP1B oligomerizes to form helical filaments by itself, it generates flexible structures with moderate membrane curvature specificity[33][36][43][56]. However, the lumenal cavity of CHMP1B filaments possesses a strongly positively charged interior lined with basic amino acids, particularly lysine and arginine residues, while maintaining an electronegative exterior surface[9][12][56]. This electrostatic architecture enables specific recognition and stabilization of negatively charged membrane surfaces, positioning CHMP1B filaments to interact with acidic phospholipid headgroups from the cytoplasmic face of the membrane, thereby wrapping around the external surface of positively curved membrane tubules[9][12][24][56].

This positive-curvature specificity contrasts sharply with canonical ESCRT-III proteins like CHMP4, which polymerize into tight, rigid helical tubes with negatively charged interiors that fill negatively curved membrane invaginations[9][24][43][56]. The functional consequence is that CHMP1B contributes to distinct cellular membrane remodeling events compared to other ESCRT-III proteins, particularly processes involving the scission of tubular endosomal membrane projections that extend into the cytoplasm[9][12][17][24].

Cellular Localization and Subcellular Distribution

Endosomal and Vesicular Localization

CHMP1B exhibits predominantly cytoplasmic distribution under steady-state conditions, where it exists in a monomeric, autoinhibited conformation[2][14][26]. However, upon cell stimulation or during specific phases of the cell cycle, CHMP1B undergoes rapid translocation to distinct endosomal compartments where it participates in active membrane remodeling processes[14][26][35][38][48]. Early endosomal markers such as EEA1 show limited overlap with CHMP1B localization, whereas CHMP1B shows more robust colocalization with late endosomal markers including Lamp1, suggesting preferential recruitment to MVBs and late endosomal compartments where degradative cargo sorting occurs[14][26][38][48].

Recent live-cell imaging studies with improved spatial resolution have revealed that CHMP1B occupies discrete subdomains on early/sorting endosomes, distinct from compartments marked by classical MVB sorting machinery components[17][37][40]. Using fluorescently labeled transferrin receptor tracking and high-resolution microscopy, researchers identified that CHMP1B colocalizes with SNX15, a sorting nexin that regulates endosomal recycling, at distinct endosomal subdomains separate from those marked by HRS (a component of the ESCRT-I complex) or VPS35 (a retromer component)[17][37][40]. This spatial segregation suggests that CHMP1B participates in specific recycling pathways originating from sorting endosomes rather than contributing uniformly to all MVB-mediated cargo sorting processes[17][37][40].

Midbody Localization During Cytokinesis

Beyond its endosomal roles, CHMP1B undergoes striking relocalization to the midbody during cytokinesis, the final stage of cell division wherein dividing cells remain connected by a membrane bridge containing concentrated microtubules[11][21][55][58]. CHMP1B localizes prominently to midbodies in dividing HeLa cells, where it colocalizes with the microtubule-severing protein spastin and other ESCRT components including CHMP5[58]. The functional significance of this midbody localization relates to the process of abscission, wherein the membrane bridge connecting daughter cells must be severed to complete cell division[11][21][55][58].

The recruitment of CHMP1B to midbodies appears to be essential for proper spastin localization, as knockdown of CHMP1B results in dramatic reduction of spastin at midbodies despite spastin remaining unaffected at other cellular locations[58]. These findings indicate that CHMP1B actively recruits spastin to the midbody through direct binding of spastin's MIT domain to CHMP1B's MIM motif, thereby establishing a functional nexus between ESCRT machinery and the microtubule-severing machinery required for cytokinetic abscission[21][58].

Lipid Droplet-Peroxisome Contact Sites

A emerging but less well-characterized localization of CHMP1B involves membrane contact sites between lipid droplets and peroxisomes[9][13][16]. The membrane-bound AAA ATPase spastin isoform (M1 spastin) recruited to lipid droplets via an N-terminal hydrophobic hairpin motif recruits CHMP1B and IST1 to lipid droplet membranes through its MIT domain[13][16]. At these contact sites, the IST1-CHMP1B copolymer appears to facilitate membrane remodeling that facilitates fatty acid trafficking from lipid droplets to peroxisomes for oxidative catabolism[13][16]. This represents a relatively recently discovered function of CHMP1B in lipid metabolism and cellular bioenergetics, expanding understanding of ESCRT-III roles beyond classical endosomal trafficking[13][16].

Protein-Protein Interactions and Regulatory Mechanisms

VPS4 Interaction and MIT-MIM Recognition

CHMP1B engages in high-affinity interactions with VPS4 ATPases through specific recognition of the VPS4 MIT (microtubule-interacting and trafficking) domain by the CHMP1B MIM (MIT-interacting motif) located at its C-terminus[2][21][58]. This MIT-MIM interaction has been structurally characterized, revealing that CHMP1B MIM residues including leucine 188 and leucine 192 insert into hydrophobic pockets within the VPS4 MIT domain[21]. The interaction surface measures approximately 12 × 22 Ångströms and involves burial of approximately 1,200 Ų of surface area, consistent with the measured binding affinity of approximately 33 μM[21]. This interaction serves as the primary recruitment mechanism enabling VPS4 localization to membrane-associated ESCRT-III filaments.

VPS4 functions as an AAA ATPase that powers energy-dependent disassembly of ESCRT-III filaments through ATP hydrolysis, thereby recycling ESCRT-III subunits back into the cytoplasmic pool and driving progressive membrane fission[12][24][56][57]. The MIT-MIM interaction enables VPS4 hexamerization around CHMP1B-containing filaments and facilitates conformational changes within these filaments that progressively constrict membranes. The sequential action of VPS4-mediated filament remodeling and subunit exchange generates forces sufficient to drive membrane fission, though the precise molecular mechanism remains an area of active investigation[12][24][56][57].

Spastin MIT Domain Recognition with High Affinity

While CHMP1B interacts with VPS4 through its MIM motif, the protein also engages in even higher-affinity interaction with spastin, the microtubule-severing AAA ATPase encoded by the SPG4 gene[21][58][60]. The spastin MIT domain recognizes CHMP1B with a dissociation constant of approximately 12 μM, approximately 2.75-fold higher affinity than VPS4 MIT domain binding[21]. Structural analysis revealed that the spastin MIT domain utilizes a distinct binding surface compared to VPS4, employing a groove formed between helices α1 and α3 of the MIT domain rather than the α2-α3 groove used by VPS4[21].

This dual-function capacity of the CHMP1B MIM for selective binding to both VPS4 and spastin represents a remarkable example of molecular adaptation wherein the same CHMP1B sequence achieves specificity for distinct protein partners through recognition of distinct binding surfaces on their respective MIT domains[21][58]. The bifunctional MIM permits CHMP1B to alternate between interaction with VPS4 (primarily involved in reverse-topology ESCRT processes at MVBs) and interaction with spastin (primarily involved in endosomal recycling and cytokinetic abscission), thereby enabling context-dependent protein partnerships[21][58].

IST1 Partnership and Copolymer Formation

Perhaps the most functionally significant interaction involving CHMP1B is its association with IST1 (increased sodium tolerance 1), the CHMP8-encoded ESCRT-III protein that mediates normal-topology membrane remodeling[9][11][12][17][24][32][33][37][40]. CHMP1B and IST1 interact through distinct surfaces compared to their respective interactions with other ESCRT-III proteins. The CHMP1B-IST1 interaction involves a groove formed by the autoinhibitory helix α5 of IST1 against the core domain helix α2, creating a high-affinity binding site with multiple contributing residues[11][32][33].

The functional consequence of IST1-CHMP1B interaction is assembly into copolymeric filaments rather than separate homopolymers[9][24][33][36]. These copolymers exhibit extraordinary structural properties: cryo-EM reconstructions at near-atomic resolution reveal that IST1 and CHMP1B form parallel double-stranded helical filaments with 1:1 stoichiometry, wherein IST1 comprises the external strand while CHMP1B forms the internal strand[9][24][33][36]. The two strands interweave extensively, with CHMP1B helix α4 binding to multiple segments of the IST1 N-terminal domain helix α1, creating a tightly interlocked structure. Additionally, the CHMP1B C-terminal MIM region "snorkels" from the inner strand to the outer strand, where it packs antiparallel against IST1 helix α5 at the closed IST1 interface[24][33].

IST1-CHMP1B Copolymer Formation and Unique Functions

Sequential Polymerization Mechanism and Membrane Constriction

Detailed structural and biochemical studies have illuminated a remarkable sequential polymerization mechanism whereby CHMP1B initially polymerizes into flexible single-stranded filaments that wrap around target membranes to induce moderate curvature, followed by subsequent IST1 assembly onto CHMP1B to progressively constrict the membrane[9][33][36]. Initial CHMP1B assembly generates membrane-bound helical filaments with right-handed chirality, moderate outer diameter (~24 nm), and moderate lumenal diameter (~12 nm at the inner leaflet) that wrap around the external surface of positively curved membrane tubules[33][36][43][56]. The lumenal cavity possesses strong positive charge capable of shaping negatively charged phospholipid membranes into tube-like configurations[9][24][33][56].

The flexibility of CHMP1B filaments enables variable curvature, with both right-handed and left-handed helical orientations observed, and adjustable helical parameters accommodated through motion at specific hinge points including the "elbow" joint between helices α3 and α4 and the "wrist" joint between α2 and α3[33][36][43][56]. This conformational flexibility contrasts sharply with the rigidity of canonical ESCRT-III filaments composed of CHMP4, enabling CHMP1B to adapt to variable membrane geometries[9][24][33][56].

Upon IST1 addition, a second strand assembles atop CHMP1B through an intricate network of protein-protein interactions, driving further membrane constriction[9][33][36]. The sequential IST1 polymerization reduces the lumenal inner leaflet diameter from approximately 12 nanometers in CHMP1B-only filaments to approximately 4.8 nanometers in IST1-CHMP1B copolymers (right-handed configuration) or 4.4 nanometers in the left-handed configuration[33][36]. This constriction brings the membrane nearly to the fission point, wherein opposing bilayer leaflets approach hemi-fusion geometry[33][36].

Concurrent with progressively tighter membrane constriction, sequential bilayer thinning occurs as CHMP1B and IST1 apply constrictive forces to the underlying membrane[9][33][36]. Measurements of phosphate-to-phosphate distances between outer and inner membrane leaflets revealed progressive compression: relaxed liposomes maintained approximately 31 Ångströms thickness, CHMP1B-constricted membranes compressed to 29.9 Ångströms, and IST1-CHMP1B copolymers further compressed membranes to 28.6 or 28.4 Ångströms (right- and left-handed respectively)[36]. This progressive bilayer thinning dramatically reduces the energetic barrier to membrane fission by bringing the membrane to the critical geometry for spontaneous fission[9][33][36].

Normal-Topology Membrane Remodeling in Endosomal Recycling

While most canonical ESCRT-III complexes mediate reverse-topology membrane scission (wherein membrane invaginations bud away from the cytoplasm into the cytoplasm), the IST1-CHMP1B copolymer uniquely facilitates normal-topology membrane scission wherein tubular membrane projections bud away from the cytoplasm into the cytoplasm, with ESCRT proteins coating the external membrane surface[9][12][17][24][22][52][56]. This functional dichotomy has been functionally confirmed through targeted chemical inhibition: the compound Tantalosin specifically disrupts IST1-CHMP1B interaction while leaving other ESCRT-III interactions intact, enabling selective interrogation of IST1-CHMP1B function[22][27][52][59].

Treatment with Tantalosin rapidly blocks transferrin receptor (TfR) recycling from early/sorting endosomes, causing accumulation of transferrin in stalled sorting endosomal compartments[22][27][52][59]. This recycling defect is selective for pathways mediated by the IST1-CHMP1B complex, as Tantalosin does not inhibit multivesicular body cargo sorting, extracellular vesicle biogenesis, or cytokinetic abscission[22][27][52][59]. These functional findings establish that IST1-CHMP1B copolymers mediate selective recycling endosomal cargo trafficking through normal-topology membrane remodeling processes distinct from reverse-topology scission[17][22][27][37][40][52][59].

Further analysis demonstrated that IST1 localizes to early/sorting endosomes in partnership with SNX15 and CHMP1B at endosomal subdomains distinct from those marked by HRS or VPS35, establishing a specialized compartmental identity[17][37][40]. Depletion of IST1 or CHMP1B individually increases both the frequency and persistence of tubular carriers emerging from early/sorting endosomes, consistent with impaired tubule scission[17][37][40]. The IST1-CHMP1B complex thus mediates scission of tubulovesicular carriers enriched in recycling cargo, directing transferrin receptor and mannose 6-phosphate receptor back toward the endocytic recycling compartment and plasma membrane[17][37][40].

Friction-Driven Membrane Scission Independent of VPS4

A surprising recent discovery emerged from in vitro reconstitution studies demonstrating that the IST1-CHMP1B complex is capable of membrane scission through a friction-driven mechanism that does not require VPS4 or spastin AAA ATPase activity[57]. Using optical trap-based nanotube pulling assays, researchers reconstituted membrane fission with IST1-CHMP1B filaments coating the external surface of lipid bilayer nanotubes, finding that membranes spontaneously fission following a characteristic time course[57]. Importantly, this scission occurred without addition of ATP or ATPase activity, distinguishing it from classical VPS4-dependent ESCRT-mediated membrane fission[57].

The proposed mechanism involves progressive friction-driven membrane scission wherein the CHMP1B-IST1 copolymer coat constricts the membrane while simultaneously applying viscous drag forces that progressively thin the bilayer, ultimately driving spontaneous membrane fission without requiring additional ATP hydrolysis[57]. This represents a potentially more primitive membrane scission mechanism compared to the VPS4-dependent processes involved in MVB biogenesis, perhaps reflecting evolutionary optimization for distinct membrane remodeling contexts[12][24][56][57].

In contrast, VPS4 addition to these systems resolubilized CHMP1B and IST1 from the membrane without promoting membrane fission, indicating that VPS4-mediated ESCRT disassembly occurs via a distinct mechanism from friction-driven scission[57]. Spastin similarly colocalized with CHMP1B-enriched sites but did not disassemble the coat or promote scission[57]. These findings suggest that while VPS4 and spastin interact with CHMP1B through its MIM domain, their primary roles may involve regulation of membrane constriction dynamics and recruitment to specific cellular sites rather than direct catalysis of membrane fission[57].

Role in Distinct Cellular Processes

HIV-1 Virion Release and Budding

CHMP1B contributes to HIV-1 budding, though its role is less essential than other ESCRT components[8]. Co-depletion of CHMP1A and CHMP1B reduced HIV-1 virus release modestly (>2-fold), whereas co-depletion of CHMP2A and CHMP2B or CHMP4A, CHMP4B, and CHMP4C produced dramatically more severe defects (95-fold and 166-fold reductions respectively)[8]. Individual CHMP1B depletion reduced viral titers 8-fold, making it a moderate contributor to HIV budding[8]. The mechanisms likely involve CHMP1B's capacity to mediate reverse-topology membrane scission required for completion of virion release, though this process is partially redundant with other ESCRT-III members[8].

HIV-1 budding specifically requires CHMP2A and CHMP4B interaction, as mutations disrupting this interface severely inhibit virus release[8]. In contrast, CHMP1 proteins appear to have accessory roles, potentially facilitating membrane deformation or cooperating with other ESCRT components to enhance efficiency of virion scission[8]. The relative redundancy of CHMP1 function in HIV budding compared to other ESCRT-III members reflects its more specialized role in normal-topology membrane remodeling, which may only partially contribute to the reverse-topology scission required for virion release[8].

Cytokinetic Abscission and Midbody Dynamics

During cytokinesis, CHMP1B localizes to the midbody and plays a demonstrated role in recruitment of the microtubule-severing protein spastin[21][58][59]. CHMP1B depletion significantly reduces spastin localization to midbodies (from 82.3% in control cells to 39.0% in CHMP1B-depleted cells), indicating that CHMP1B actively recruits spastin through MIT-MIM interaction[58]. However, IST1-CHMP1B copolymer-mediated normal-topology membrane scission does not appear to be required for cytokinetic abscission, as Tantalosin treatment (which specifically inhibits IST1-CHMP1B interaction) does not impair cytokinesis[22][27][52][59].

This apparent paradox suggests that CHMP1B's role in cytokinesis primarily involves recruitment and scaffolding functions for spastin and other ESCRT components rather than direct participation in normal-topology membrane scission[21][52][59]. The IST1-CHMP1B copolymer may serve additional reverse-topology scission roles during cytokinesis, or CHMP1B functions in other contexts through interaction with distinct partners[52][59]. Future studies with more specific inhibitors targeting individual CHMP1B interaction surfaces may clarify these distinctions[21][52][59].

Endosomal Recycling and Receptor Trafficking

As detailed above, IST1-CHMP1B complexes mediate endosomal recycling of cargo proteins including transferrin receptor and mannose 6-phosphate receptor, maintaining proper cellular localization of receptors and trafficking machinery[17][37][40][22][27][52][59]. This process involves tubule scission from sorting endosomes, enabling rapid recycling of these cargo-laden tubules back to the plasma membrane or to the endocytic recycling compartment[17][37][40]. Disruption of IST1-CHMP1B function causes cargo missorting and accumulation in peripheral endosomes, underscoring the importance of this complex for proper cellular trafficking[17][37][40][22][27][52][59].

Interestingly, recent studies identified that IST1 depletion also enhances rapid recycling of transferrin receptor to the plasma membrane via peripheral endosomes enriched in clathrin adaptor AP-1, suggesting that IST1 normally suppresses fast-recycling pathways to favor slower recycling through the recycling endosomal compartment[17][40]. This suggests a more nuanced role for IST1-CHMP1B in fine-tuning endosomal traffic distribution rather than simply mediating univocal trafficking to one destination[17][40].

Fatty Acid Trafficking and Lipid Droplet Biology

An emerging function for CHMP1B involves fatty acid trafficking from lipid droplets to peroxisomes, a process mediated through the M1 spastin-CHMP1B-IST1 complex at membrane contact sites between these organelles[13][16]. M1 spastin recruits CHMP1B and IST1 via its MIT domain, and this recruitment promotes fatty acid transport from lipid droplets toward peroxisomes for β-oxidation[13][16]. Importantly, M1 spastin-mediated fatty acid trafficking reduces peroxidated lipids within lipid droplets, suggesting a protective role against oxidative stress[13][16].

This function represents a relatively recently discovered role of ESCRT-III proteins in metabolic processes beyond endosomal sorting. The IST1-CHMP1B copolymer at LD-peroxisome contact sites likely facilitates membrane remodeling or tethering that enables efficient lipid transfer, though detailed molecular mechanisms remain to be established[13][16].

Regulatory Mechanisms and Post-Translational Modifications

Ubiquitination-Dependent Regulation by USP8

Recent studies have revealed that CHMP1B undergoes dynamic ubiquitination in response to growth factor stimulation, with ubiquitin removal mediated by the USP8 deubiquitinase (also designated UBPY)[14][26][35][38][48][51]. CHMP1B contains multiple lysine residues susceptible to ubiquitination, with lysine 87 and lysine 90 representing major ubiquitination sites located within the flexible linker region between helices α2 and α3[26][35][38][48][51]. This linker region becomes helical in the active polymerized state, suggesting that ubiquitination may preferentially target the inactive monomeric form while deubiquitination facilitates polymerization[26][35][38][48][51].

Upon epidermal growth factor (EGF) stimulation of cells, endogenous CHMP1B undergoes rapid ubiquitination followed by accumulation at cellular membranes, particularly at late endosomal compartments marked by Lamp1[14][26][35][38][48][51]. This ubiquitination-dependent membrane recruitment occurs with rapid kinetics, peaking within minutes of EGF stimulation[14][26][35][38][48][51]. The USP8 deubiquitinase interacts with CHMP1B through the USP8 MIT domain binding to the CHMP1B C-terminal MIM region, an interaction localized to late endosomes[14][26][35][38][48][51].

Functionally, ubiquitination of CHMP1B is required for proper EGFR degradation following EGF stimulation. Mutation of the four major lysine ubiquitination sites (CHMP1B-4K>R) renders the protein non-functional in EGFR trafficking, as this mutant cannot rescue defects in EGFR degradation kinetics observed in CHMP1B-depleted cells[14][26][38][48][51]. CHMP1B-silenced cells show delayed EGFR degradation compared to control cells, with EGFR remaining at plasma membranes longer before degradation[14][26][38][48][51]. Reconstitution with wild-type CHMP1B restores normal EGFR degradation kinetics, whereas the non-ubiquitinatable CHMP1B-4K>R mutant fails to rescue this defect[14][26][38][48][51].

The proposed mechanism suggests that CHMP1B ubiquitination serves as a temporal checkpoint controlling the spatial and temporal localization of CHMP1B polymerization activity at endosomal membranes in response to signaling inputs[14][26][35][38][48][51]. Ubiquitination may increase local CHMP1B concentration at membranes through enhanced recruitment, or alternatively may promote the conformational transition from closed monomeric to open polymerized states[14][26][35][38][48][51]. The catalytic deubiquitination by USP8 provides a subsequent inactivation or recycling step, enabling dynamic regulation of CHMP1B activity[14][26][35][38][48][51].

Autoinhibition and Activation Mechanisms

CHMP1B, like other ESCRT-III proteins, exists in equilibrium between autoinhibited and activated conformational states[32][35][48]. The cytoplasmic monomeric CHMP1B adopts a closed conformation wherein the C-terminal region including helices α5 and α6 fold back against the core domain, particularly engaging the α1-α2 hairpin[32][35][48]. This autoinhibition masks protein-protein interaction surfaces and prevents premature polymerization in the cytoplasm[32][35][48].

Activation requires conformational rearrangement triggered by membrane binding and/or interaction with upstream ESCRT components and accessory proteins[32][35][47][48]. The transition to the open state involves extension of the helices, melding of α2 and α3 into a continuous helix, and reorientation of helix α4, dramatically reorganizing approximately half of the protein structure[20][35][48][56]. This extensive conformational change represents a significant energetic transition, and regulation of this activation step controls ESCRT-III function[32][35][47][48].

Binding of the Bro1 domain-containing protein ALIX can relieve autoinhibition of Snf7 (the yeast CHMP4 ortholog), and analogous mechanisms likely apply to CHMP1B activation[47][48]. The interaction with IST1 during normal-topology membrane processes may provide an alternative activation pathway, as IST1 binding to CHMP1B stabilizes the open conformation and promotes polymerization[11][32][33][48]. The sequential timing of IST1 addition to preexisting CHMP1B polymers suggests IST1 acts as an activation scaffold, locking CHMP1B into productive polymerization configurations[33][36][48].

Disease Associations and Clinical Significance

Pontocerebellar Hypoplasia Type 8

Mutations in the CHMP1A gene (not CHMP1B itself, but the closely related paralog) cause pontocerebellar hypoplasia type 8 (PCH8), a rare neurodevelopmental disorder characterized by severe microcephaly, progressive cerebellar and pontine underdevelopment, severe developmental delay, and various neurological manifestations[31][34][15]. PCH8 differs from most other PCH subtypes by representing a non-degenerative form, with brain MRI showing profound pontocerebellar hypoplasia with severe hypoplasia of the corpus callosum and decreased cerebral white matter volume but without evidence of progressive neurodegeneration on serial imaging[31][34][15].

While CHMP1B mutations have not been directly reported in PCH8 (which is caused by CHMP1A mutations), the functional conservation between CHMP1A and CHMP1B suggests that CHMP1B dysfunction could contribute to similar neurodevelopmental phenotypes[2][31][34][53]. The ESCRT-III pathway is essential for cell division and cytokinesis, and disruption of normal ESCRT function during neurogenesis could impair proper neural progenitor cell division and neuronal differentiation, leading to impaired brain development[31][34].

Additional CHMP-related ESCRT pathway disruptions have been identified in other PCH subtypes. PCH9 is caused by mutations in AMPD2, which encodes an adenosine monophosphate deaminase, and PCH10 is caused by CLP1 mutations, with CLP1 functioning in tRNA processing and splicing[31][34]. These findings collectively indicate that disruption of various cellular processes required for neurogenesis, including ESCRT-mediated membrane dynamics, tRNA processing, and nucleotide metabolism, converge on pontocerebellar hypoplasia phenotypes[31][34].

Hereditary Spastic Paraplegia Association

While CHMP1B itself is not directly mutated in hereditary spastic paraplegia (HSP), mutations in SPAST (the spastin-encoding gene) are the most common genetic cause of autosomal dominant HSP[21][58][60]. Because spastin recruits to CHMP1B through their high-affinity MIT-MIM interaction, proper CHMP1B function is presumably required for spastin-mediated microtubule dynamics and cellular processes involving spastin[21][58][60].

Spastin mutations causing HSP may impair binding to CHMP1B or other binding partners, disrupting normal ESCRT-mediated endosomal recycling or cytokinetic processes[21][58][60]. The specificity of the CHMP1B-spastin interaction and its higher affinity compared to other protein-protein interactions in this pathway suggests it represents a key functional interface, and disruption could contribute to HSP pathogenesis[21][58][60].

Evolutionary Conservation and Structural Insights

Conservation Across Eukaryotic Lineages

CHMP1B belongs to the highly conserved SNF7 family of ESCRT-III proteins, with orthologs present across eukaryotic evolution from single-celled protists through plants, fungi, and animals[2][5][7][53]. The fundamental architecture of CHMP1B, including the core helical domain and the C-terminal MIM motif, is conserved across these diverse eukaryotic lineages, indicating that this protein represents an ancient component of eukaryotic membrane trafficking machinery[2][5][7][53].

Comparison of CHMP1B sequences across organisms reveals high sequence conservation within the core domain and the MIM region, with greater sequence divergence in the linker regions and peripheral elements[2][5][53]. This conservation pattern is consistent with functional constraints on the core domain structure and interaction surfaces, while permitting regulatory variation through divergence of peripheral elements[2][5][53].

In plants, CHMP1 orthologs were shown to be essential for developmental processes, with double mutants lacking CHMP1A and CHMP1B displaying severe developmental defects and embryonic lethality[29]. The conservation of CHMP1 function in MVB biogenesis and the involvement in developmental processes across plant and animal kingdoms indicates that CHMP1B's role in regulated protein degradation and recycling represents a fundamental requirement for multicellular development[29].

Structural Homology to BAR Domain Proteins

A striking evolutionary insight has emerged from structural comparison of IST1-CHMP1B copolymers with BAR (Bin/Amphiphysin/Rvs) domain proteins, a distinct protein family that also mediates normal-topology membrane tubulation and scission[12][24][56]. BAR domain proteins form banana-shaped dimeric structures with positively charged cavities that interact with negatively charged membrane surfaces to stabilize positive membrane curvature[12][24][56]. The IST1-CHMP1B copolymer exhibits analogous organization, with IST1 and CHMP1B assembling into tubular structures with positively charged lumens capable of interacting with acidic phospholipids to stabilize positive curvature[9][12][24][56].

This convergent evolution of structurally distinct protein systems (ESCRT-III versus BAR domains) toward similar functional outcomes (normal-topology membrane remodeling) provides strong evidence that the physical requirements of this cellular process constrain evolutionary solutions to a limited set of mechanisms[12][24][56]. The discovery that ESCRT-III proteins can mediate both reverse and normal-topology membrane scission through distinct protein combinations (reverse-topology: canonical ESCRT-III members; normal-topology: IST1-CHMP1B) suggests evolutionary optimization of the ESCRT pathway for diverse membrane remodeling contexts[12][24][56].

Conclusion

CHMP1B represents a multifunctional ESCRT-III component that coordinates diverse cellular membrane remodeling processes through dynamic assembly into homo- and heteropolymeric filaments with distinct membrane curvature specificities and topological preferences. The protein's central role in MVB biogenesis and intraluminal vesicle formation reflects its primary characterized function in endosomal cargo sorting, whereby ubiquitinated cargo destined for lysosomal degradation is segregated into ILVs through CHMP1B-mediated membrane scission[2][14][26][35][38]. However, emerging evidence reveals CHMP1B's participation in equally important but less characterized processes including normal-topology endosomal recycling through IST1-CHMP1B copolymer formation, cytokinetic abscission through spastin recruitment, and metabolic processes including lipid trafficking at lipid droplet-peroxisome contact sites[9][13][16][17][21][37][40][58].

The remarkable structural and functional properties of CHMP1B—its conformational flexibility, positive membrane curvature specificity, high-affinity dual interaction capacity with both VPS4 and spastin, dynamic ubiquitination-dependent regulation, and capacity for sequential polymerization with IST1—enable this single protein to participate in multiple distinct cellular processes while maintaining proper specificity and regulation[9][12][21][24][33][35][36][48][56][57][58]. The recent advances in cryo-EM structural biology have provided unprecedented atomic-resolution insights into CHMP1B filament architecture and membrane interaction mechanisms, establishing molecular foundations for understanding ESCRT-III function[9][33][36][43][56].

Future research directions should focus on elucidating the precise molecular mechanisms through which CHMP1B and IST1 catalyze friction-driven membrane fission, determining how post-translational modifications including ubiquitination regulate CHMP1B activity in response to distinct cellular signals, characterizing the roles of CHMP1B in understudied processes including lipid droplet biology and nuclear envelope dynamics, and exploring therapeutic implications of ESCRT pathway modulation for diseases including cancer, viral infection, and neurodevelopmental disorders[12][22][27][31][34][52][57][59]. The chemical inhibitor Tantalosin has proven valuable for selectively interrogating IST1-CHMP1B complex function, and development of additional selective inhibitors for distinct ESCRT-III complexes promises powerful tools for functional dissection of the ESCRT pathway[22][27][52][59]. Understanding CHMP1B biology thus provides insights into fundamental cell biological processes and potential therapeutic targets for numerous human diseases.

Citations

https://www.ncbi.nlm.nih.gov/gene/57132
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CHMP1B
https://amigo.geneontology.org/amigo/gene_product/UniProtKB:Q7LBR1
https://www.uniprot.org/uniprotkb/Q7LBR1/entry
https://www.abcam.com/en-mc/targets/chmp1b/14547
https://www.uniprot.org/uniprotkb/Q9HD42/entry
https://pmc.ncbi.nlm.nih.gov/articles/PMC3070458/
https://pmc.ncbi.nlm.nih.gov/articles/PMC7343221/
https://www.molbiolcell.org/doi/10.1091/mbc.e08-05-0475
https://pmc.ncbi.nlm.nih.gov/articles/PMC6241870/
https://pmc.ncbi.nlm.nih.gov/articles/PMC6683741/
https://pmc.ncbi.nlm.nih.gov/articles/PMC6033466/
https://www.orpha.net/en/disease/detail/324569
https://pubmed.ncbi.nlm.nih.gov/31227594/
https://pmc.ncbi.nlm.nih.gov/articles/PMC11027954/
https://rarediseases.info.nih.gov/diseases/17488/pontocerebellar-hypoplasia-type-8
https://pmc.ncbi.nlm.nih.gov/articles/PMC4720517/
https://pmc.ncbi.nlm.nih.gov/articles/PMC2593743/
https://www.pnas.org/doi/10.1073/pnas.2317680121
https://pubmed.ncbi.nlm.nih.gov/24753138/
https://anatomypubs.onlinelibrary.wiley.com/doi/full/10.1002/dvdy.24140
https://pmc.ncbi.nlm.nih.gov/articles/PMC2671707/
https://pubmed.ncbi.nlm.nih.gov/38635626/
https://pmc.ncbi.nlm.nih.gov/articles/PMC6003036/
https://pmc.ncbi.nlm.nih.gov/articles/PMC2712734/
https://rarediseases.org/rare-diseases/pontocerebellar-hypoplasia/
https://pubmed.ncbi.nlm.nih.gov/32251413/
https://pubmed.ncbi.nlm.nih.gov/37926552/
https://academic.oup.com/function/article/6/2/zqaf005/7979294
https://pubmed.ncbi.nlm.nih.gov/36872252/
https://www.science.org/doi/10.1126/science.aad8305
https://pmc.ncbi.nlm.nih.gov/articles/PMC4815105/
https://pmc.ncbi.nlm.nih.gov/articles/PMC7390632/
https://elifesciences.org/articles/15507
https://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1007456
https://pmc.ncbi.nlm.nih.gov/articles/PMC4676514/
https://pmc.ncbi.nlm.nih.gov/articles/PMC11047075/
https://www.proteinatlas.org/ENSG00000255112-CHMP1B
https://pmc.ncbi.nlm.nih.gov/articles/PMC5488711/
https://pmc.ncbi.nlm.nih.gov/articles/PMC5198518/
https://www.pnas.org/doi/10.1073/pnas.2204536119
https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.13075

📚 Additional Documentation

Notes

(CHMP1B-notes.md)

CHMP1B Annotation Review Notes

Gene Overview

CHMP1B (Charged Multivesicular Body Protein 1B) is an ESCRT-III complex component with multiple cellular roles.

Core Functions (from deep research)

ESCRT-III component for MVB formation and ILV biogenesis - mediates reverse-topology membrane scission for cargo sorting to lysosomes
Normal-topology membrane scission (with IST1 partner) - mediates endosomal recycling (transferrin receptor, M6PR)
Cytokinetic abscission - recruits spastin to midbody for final cell division step
Plasma membrane repair - ESCRT machinery recruited to membrane wounds
Viral budding - HIV-1 release (moderate role, less essential than CHMP2/CHMP4)
Autophagy - required for autophagosome maturation and fusion with lysosomes

Key Evidence

Peripherally associated ESCRT-III component [UniProt Q7LBR1]
Forms IST1-CHMP1B copolymers for normal-topology scission [deep research]
Interacts with VPS4 ATPases for ESCRT-III disassembly
Interacts with spastin MIT domain for midbody recruitment PMID:18997780
Required for EGFR degradation, regulated by USP8-mediated ubiquitination
Localizes to: late endosomes, MVB membranes, midbodies, autophagosomes

Annotation Review Strategy

ACCEPT: Core ESCRT-III functions with strong experimental evidence
MODIFY: Terms that are too general or need specificity
KEEP_AS_NON_CORE: Pleiotropic/secondary functions with decent evidence
REMOVE/MARK_AS_OVER_ANNOTATED: Weak IEA annotations, especially those without strong lit support
Avoid "protein binding" - not informative, replace with specific MF terms

Key Papers to Reference

PMID:17984323 - Autophagy, MVB function in protein aggregates
PMID:20616062 - Centrosome and spindle maintenance, cytokinesis
PMID:24482116 - Plasma membrane repair
PMID:26040712 - Spastin recruitment, spindle disassembly
PMID:26040713 - Nuclear envelope reformation
PMID:24878737 - ESCRT-III structure, HIV budding
PMID:16554368 - MVB sorting, EGFR degradation

REVIEW COMPLETED - Summary

Date: 2025-11-23
Status: COMPLETE

Summary Statistics

Total annotations reviewed: 117
ACCEPT: 66 annotations (core ESCRT-III functions)
KEEP_AS_NON_CORE: 17 annotations (mitotic/kinetochore functions)
MODIFY: 10 annotations (terms needing replacement)
REMOVE: 4 annotations (extracellular exosome contaminants, inappropriate yeast terms)

Key Decisions

Accepted core functions:
MVB/late endosome localization and membrane remodeling
Autophagosome maturation and lysosome transport
Midbody abscission and nuclear envelope reformation
Plasma membrane repair
Cargo sorting via MVB pathway
MIT domain binding (highly specific MF)
Identical protein binding (ESCRT-III oligomerization)
Non-core but valid functions:
Kinetochore/mitotic functions (chromosome alignment, spindle regulation)
Centrosome duplication regulation
HIV-1 budding (moderate contributor)
Modified annotations:
Replaced generic "protein transport" with specific MVB sorting terms
Replaced yeast-specific "vacuole" terms with mammalian "lysosome" terms
Recommended replacing generic "protein binding" IPIs with specific binding terms
Removed annotations:
3x extracellular exosome (HDA) - likely ESCRT contamination in proteomics
Vacuolar transport (yeast IEA) - inappropriate for human

Core Molecular Functions Identified

GO:0090541 (MIT domain binding): High-affinity binding to VPS4 and spastin for ESCRT-III regulation
GO:0042802 (identical protein binding): Self-assembly into helical filaments for membrane constriction

Notable Insights

CHMP1B exhibits dual topology specificity - unique among ESCRT-III proteins
Forms IST1-CHMP1B copolymers specifically for normal-topology scission
Regulated by USP8-mediated deubiquitination in response to growth factors
Bifunctional MIM motif enables context-dependent VPS4 vs spastin recruitment

📄 View Raw YAML

id: Q7LBR1
gene_symbol: CHMP1B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: CHMP1B is an ESCRT-III complex component that mediates membrane
  remodeling processes with dual topology specificity. It functions in
  reverse-topology membrane scission for MVB formation and cargo sorting to
  lysosomes, and in normal-topology membrane scission via IST1-CHMP1B copolymers
  for endosomal recycling. CHMP1B recruits spastin to midbodies for cytokinetic
  abscission, participates in plasma membrane repair and autophagosome
  maturation, and has moderate roles in HIV-1 budding. The protein is regulated
  by USP8-mediated deubiquitination and localizes to late endosomes, MVB
  membranes, midbodies, autophagosomes, nuclear pore, and kinetochores.
existing_annotations:
  - term:
      id: GO:0005771
      label: multivesicular body
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHMP1B is a core ESCRT-III component that localizes to MVBs where
        it mediates intraluminal vesicle formation and cargo sorting.
      action: ACCEPT
      reason: MVB localization is a core function of CHMP1B. The deep research
        extensively describes CHMP1B's role in MVB formation and ILV biogenesis
        with colocalization to late endosomal/MVB compartments marked by Lamp1.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
          supporting_text: CHMP1B shows more robust colocalization with late
            endosomal markers including Lamp1, suggesting preferential
            recruitment to MVBs and late endosomal compartments where
            degradative cargo sorting occurs
        - reference_id: file:human/CHMP1B/CHMP1B-deep-research-falcon.md
          supporting_text: See deep research file for comprehensive analysis
  - term:
      id: GO:0015031
      label: protein transport
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: This term is overly broad and uninformative for CHMP1B's specific
        function. Should be replaced with more specific MVB cargo sorting and
        endosomal trafficking terms.
      action: MODIFY
      reason: While CHMP1B does participate in protein transport, this IBA
        annotation is too general. CHMP1B specifically mediates cargo sorting
        via MVB pathway and endosomal recycling, not general protein transport.
      proposed_replacement_terms:
        - id: GO:0032509
          label: endosome transport via multivesicular body sorting pathway
        - id: GO:0071985
          label: multivesicular body sorting pathway
  - term:
      id: GO:0032509
      label: endosome transport via multivesicular body sorting pathway
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Core ESCRT-III function for CHMP1B in mediating cargo transport
        through the MVB pathway for lysosomal degradation.
      action: ACCEPT
      reason: This IBA correctly captures CHMP1B's central role in the MVB
        sorting pathway. Literature extensively documents CHMP1B's function in
        cargo sorting and ILV formation.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
          supporting_text: The primary established function of CHMP1B derives
            from its participation in multivesicular body (MVB) formation, a
            critical process in which cargo-containing membrane invaginations at
            the limiting membrane of late endosomal compartments undergo
            scission to generate intraluminal vesicles (ILVs)
  - term:
      id: GO:0045324
      label: late endosome to vacuole transport
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: This term uses yeast-specific terminology. In mammals CHMP1B
        mediates late endosome to lysosome transport.
      action: MODIFY
      reason: The term uses "vacuole" which is yeast-specific nomenclature. For
        human CHMP1B, the equivalent process is late endosome to lysosome
        transport (GO:1902774), which is also annotated.
      proposed_replacement_terms:
        - id: GO:1902774
          label: late endosome to lysosome transport
  - term:
      id: GO:0000815
      label: ESCRT III complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHMP1B is a core structural component of the ESCRT-III complex.
        This is fundamental to all CHMP1B functions.
      action: ACCEPT
      reason: CHMP1B is definitionally an ESCRT-III component belonging to the
        SNF7 family. This is supported by extensive structural and functional
        evidence.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-uniprot.txt
          supporting_text: Probable peripherally associated component of the
            endosomal sorting required for transport complex III (ESCRT-III)
        - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
          supporting_text: Within the ESCRT-III complex, CHMP1B belongs to the
            CHMP1 subfamily, which includes the related protein CHMP1A and
            exhibits distinct functional properties compared to other ESCRT-III
            members such as the CHMP2, CHMP3, and CHMP4 families
  - term:
      id: GO:0000776
      label: kinetochore
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: IEA annotation supported by experimental IDA evidence
        (PMID:26040712). Valid but non-core mitotic localization.
      action: KEEP_AS_NON_CORE
      reason: Although there is direct experimental evidence (IDA) from
        PMID:26040712 showing CHMP1B localization to kinetochores during
        mitosis, this represents a non-core pleiotropic function, not the
        primary ESCRT-III role.
  - term:
      id: GO:0001778
      label: plasma membrane repair
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: IEA annotation but supported by experimental evidence
        PMID:24482116 showing ESCRT machinery requirement for plasma membrane
        repair.
      action: ACCEPT
      reason: Despite being IEA, this is supported by IDA evidence from
        PMID:24482116. The deep research confirms ESCRT machinery including
        CHMP1B is required for plasma membrane repair.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
          supporting_text: CHMP1B exhibits predominantly cytoplasmic
            distribution under steady-state conditions
  - term:
      id: GO:0005643
      label: nuclear pore
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: IEA annotation supported by experimental IDA evidence
        (PMID:26040713) for nuclear envelope reformation.
      action: ACCEPT
      reason: This IEA is backed by IDA evidence showing CHMP1B involvement in
        nuclear membrane reassembly and nuclear pore function during cell
        division.
  - term:
      id: GO:0005765
      label: lysosomal membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: IEA annotation supported by IDA evidence (PMID:17984323). CHMP1B
        localizes to lysosomal membranes during autophagy and MVB-lysosome
        fusion.
      action: ACCEPT
      reason: Supported by experimental evidence showing CHMP1B at lysosomal
        membranes, consistent with its role in MVB-lysosome fusion and
        autophagosome maturation.
  - term:
      id: GO:0005768
      label: endosome
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Broad endosomal localization term. CHMP1B localizes more
        specifically to late endosomes and MVBs rather than generic endosomes.
      action: MODIFY
      reason: While technically correct, this term is too broad. CHMP1B
        specifically localizes to late endosomes and MVBs, not early endosomes.
        More specific terms like late endosome membrane (GO:0031902) or MVB
        membrane (GO:0032585) are more appropriate.
      proposed_replacement_terms:
        - id: GO:0031902
          label: late endosome membrane
        - id: GO:0032585
          label: multivesicular body membrane
  - term:
      id: GO:0005828
      label: kinetochore microtubule
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: IEA annotation supported by IDA evidence (PMID:26040712) during
        mitosis.
      action: KEEP_AS_NON_CORE
      reason: Experimental evidence supports this localization during mitotic
        spindle disassembly and chromosome alignment, but this represents a
        non-core mitotic function, not the primary ESCRT-III role.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: CHMP1B exists in cytosol in its autoinhibited monomeric form
        before membrane recruitment.
      action: ACCEPT
      reason: Correct - CHMP1B exists as soluble cytosolic protein in
        autoinhibited state before activation and membrane recruitment.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
          supporting_text: CHMP1B exhibits predominantly cytoplasmic
            distribution under steady-state conditions, where it exists in a
            monomeric, autoinhibited conformation
  - term:
      id: GO:0007034
      label: vacuolar transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: Yeast-specific term not appropriate for human CHMP1B. The
        mammalian equivalent is lysosomal transport.
      action: REMOVE
      reason: This term is based on InterPro domain annotation but uses
        yeast-specific vocabulary ("vacuolar"). For human CHMP1B,
        lysosomal/endosomal transport terms are more appropriate.
  - term:
      id: GO:0007080
      label: mitotic metaphase chromosome alignment
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: IEA annotation supported by experimental IMP evidence
        (PMID:20616062).
      action: KEEP_AS_NON_CORE
      reason: Experimental evidence supports this function, but it represents a
        non-core pleiotropic role. CHMP1B's primary function is membrane
        remodeling; chromosome alignment is a secondary consequence of its
        mitotic roles.
  - term:
      id: GO:0015031
      label: protein transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Duplicate broad term based on UniProtKB keyword. Too general.
      action: MODIFY
      reason: This is a duplicate annotation (also present as IBA) and is overly
        broad. CHMP1B's transport functions are specific to MVB cargo sorting
        and endosomal trafficking.
      proposed_replacement_terms:
        - id: GO:0071985
          label: multivesicular body sorting pathway
  - term:
      id: GO:0030496
      label: midbody
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Midbody localization during cytokinesis is well-established and
        represents a core CHMP1B function for spastin recruitment.
      action: ACCEPT
      reason: Multiple experimental evidences (IDA) confirm midbody localization
        where CHMP1B recruits spastin for abscission.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
          supporting_text: CHMP1B undergoes striking relocalization to the
            midbody during cytokinesis, the final stage of cell division wherein
            dividing cells remain connected by a membrane bridge containing
            concentrated microtubules. CHMP1B localizes prominently to midbodies
            in dividing HeLa cells, where it colocalizes with the
            microtubule-severing protein spastin and other ESCRT components
            including CHMP5
  - term:
      id: GO:0031468
      label: nuclear membrane reassembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: IEA annotation supported by experimental IMP evidence
        (PMID:26040713).
      action: ACCEPT
      reason: Experimental evidence demonstrates CHMP1B's role in nuclear
        envelope reformation after mitosis via ESCRT-III-mediated membrane
        sealing.
  - term:
      id: GO:0031902
      label: late endosome membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Late endosome membrane is a core localization site for CHMP1B
        during MVB cargo sorting.
      action: ACCEPT
      reason: Correct localization - CHMP1B preferentially localizes to late
        endosomal membranes for MVB formation.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
          supporting_text: CHMP1B shows more robust colocalization with late
            endosomal markers including Lamp1, suggesting preferential
            recruitment to MVBs and late endosomal compartments where
            degradative cargo sorting occurs
  - term:
      id: GO:0032585
      label: multivesicular body membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Core localization site where CHMP1B mediates ILV formation.
      action: ACCEPT
      reason: MVB membrane is a central localization for CHMP1B function.
        Extensively supported by experimental IDA evidence.
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP1B has a moderate role in HIV-1 budding, less essential than
        CHMP2/CHMP4 family members.
      action: KEEP_AS_NON_CORE
      reason: CHMP1B does participate in viral budding but with lower
        essentiality (8-fold reduction) compared to CHMP2/CHMP4 (95-166 fold).
        This is a valid but non-core function.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
          supporting_text: Co-depletion of CHMP1A and CHMP1B reduced HIV-1 virus
            release modestly (>2-fold), whereas co-depletion of CHMP2A and
            CHMP2B or CHMP4A, CHMP4B, and CHMP4C produced dramatically more
            severe defects (95-fold and 166-fold reductions respectively).
            Individual CHMP1B depletion reduced viral titers 8-fold, making it a
            moderate contributor to HIV budding
  - term:
      id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the
        multivesicular body sorting pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Core CHMP1B function in sorting ubiquitinated cargo into ILVs for
        lysosomal degradation.
      action: ACCEPT
      reason: This precisely describes CHMP1B's central role in the MVB pathway
        for degrading ubiquitinated membrane proteins like activated receptor
        tyrosine kinases.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
          supporting_text: The involvement of CHMP1B in this process is
            particularly important for trafficking of ubiquitinated cargo
            destined for lysosomal degradation
  - term:
      id: GO:0046761
      label: viral budding from plasma membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Related to CHMP1B's role in HIV-1 release via ESCRT machinery.
      action: KEEP_AS_NON_CORE
      reason: CHMP1B contributes to HIV budding but it is not a core function -
        more of an accessory role compared to other ESCRT-III proteins.
  - term:
      id: GO:0051301
      label: cell division
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: CHMP1B participates in cytokinetic abscission which is part of
        cell division, but this term is too broad.
      action: MODIFY
      reason: While CHMP1B does function in cell division, the more specific
        term "midbody abscission" (GO:0061952) better captures its precise role.
      proposed_replacement_terms:
        - id: GO:0061952
          label: midbody abscission
  - term:
      id: GO:0061952
      label: midbody abscission
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP1B recruits spastin to midbodies for cytokinetic abscission -
        a well-established core function.
      action: ACCEPT
      reason: Well-supported by experimental evidence showing CHMP1B's essential
        role in recruiting spastin for membrane scission during cytokinesis.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-uniprot.txt
          supporting_text: Involved in cytokinesis. Involved in recruiting VPS4A
            and/or VPS4B and SPAST to the midbody of dividing cells
  - term:
      id: GO:0071985
      label: multivesicular body sorting pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Core pathway for CHMP1B function in cargo sorting and ILV
        biogenesis.
      action: ACCEPT
      reason: Central to CHMP1B's primary function. Well-supported by
        experimental evidence.
  - term:
      id: GO:0097352
      label: autophagosome maturation
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP1B is required for fusion of autophagosomes with lysosomes
        during autophagy.
      action: ACCEPT
      reason: Experimental evidence (IMP PMID:17984323) demonstrates CHMP1B's
        requirement for autophagosome maturation and clearance of protein
        aggregates.
      supported_by:
        - reference_id: file:human/CHMP1B/CHMP1B-uniprot.txt
          supporting_text: Functional multivesicular bodies are required for
            autophagic clearance of protein aggregates
  - term:
      id: GO:1901673
      label: regulation of mitotic spindle assembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Non-core pleiotropic function during mitosis.
      action: KEEP_AS_NON_CORE
      reason: Experimental evidence supports this but it represents a secondary
        mitotic role, not core ESCRT-III function.
  - term:
      id: GO:1902774
      label: late endosome to lysosome transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Core CHMP1B function in MVB-lysosome fusion for cargo
        degradation.
      action: ACCEPT
      reason: This correctly describes CHMP1B's role in mediating fusion of MVBs
        with lysosomes to enable degradation of sorted cargo.
  - term:
      id: GO:1904930
      label: amphisome membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Amphisomes are hybrid organelles formed by fusion of
        autophagosomes with endosomes. Valid localization.
      action: ACCEPT
      reason: Supported by experimental IDA evidence (PMID:17984323) in context
        of autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16730941
    review:
      summary: Generic protein binding term - uninformative. Actual interactions
        include CHMP1A, STAMBP, VPS4A.
      action: MODIFY
      reason: This generic term doesn't provide useful information about CHMP1B
        function. The paper identifies specific binding partners. More specific
        terms like "MIT domain binding" or "identical protein binding" are more
        informative.
      proposed_replacement_terms:
        - id: GO:0042802
          label: identical protein binding
        - id: GO:0090541
          label: MIT domain binding
      supported_by:
        - reference_id: PMID:16730941
          supporting_text: 'May 30. A systematic analysis of human CHMP protein interactions:
            additional MIT domain-containing proteins bind to multiple components
            of the human ESCRT III complex.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17711858
    review:
      summary: Generic protein binding - this paper shows UBPY/USP8 binding to
        CHMP1B. Should use more specific term.
      action: MODIFY
      reason: Paper demonstrates USP8 deubiquitinase binding to CHMP1B via MIT
        domain. More informative to annotate as MIT domain binding.
      proposed_replacement_terms:
        - id: GO:0090541
          label: MIT domain binding
      supported_by:
        - reference_id: PMID:17711858
          supporting_text: 2007 Aug 21. The MIT domain of UBPY constitutes a
            CHMP binding and endosomal localization signal required for
            efficient epidermal growth factor receptor degradation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17928862
    review:
      summary: Generic term - paper shows VPS4 ATPase binding via MIT-MIM
        interaction.
      action: MODIFY
      reason: This paper characterizes ESCRT-III recognition by VPS4 MIT
        domains. MIT domain binding is more specific.
      proposed_replacement_terms:
        - id: GO:0090541
          label: MIT domain binding
      supported_by:
        - reference_id: PMID:17928862
          supporting_text: ESCRT-III recognition by VPS4 ATPases.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19302785
    review:
      summary: Generic protein binding for USP8 interaction. Should be MIT
        domain binding.
      action: MODIFY
      reason: Paper identifies MIT domains including USP8 binding to CHMP1B.
      proposed_replacement_terms:
        - id: GO:0090541
          label: MIT domain binding
      supported_by:
        - reference_id: PMID:19302785
          supporting_text: 2009 Feb 12. Ab initio protein modelling reveals
            novel human MIT domains.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19525971
    review:
      summary: Paper on ESCRT-III autoinhibition showing IST1 and CHMP1B
        binding. Generic term uninformative.
      action: ACCEPT
      reason: Keep this as evidence of IST1-CHMP1B interaction which is critical
        for copolymer formation, though generic.
      supported_by:
        - reference_id: PMID:19525971
          supporting_text: Jun 14. Structural basis for ESCRT-III protein
            autoinhibition.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21827950
    review:
      summary: Generic term for STAMBP/AMSH recruitment to CHMP1B.
      action: ACCEPT
      reason: Documents important CHMP1B-STAMBP interaction though term is
        generic.
      supported_by:
        - reference_id: PMID:21827950
          supporting_text: Structural basis for ESCRT-III CHMP3 recruitment of
            AMSH.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21988832
    review:
      summary: Large-scale liver interactome study with STAMBP interaction.
      action: ACCEPT
      reason: Large-scale proteomic evidence for interactions, keep as
        supporting evidence.
      supported_by:
        - reference_id: PMID:21988832
          supporting_text: Toward an understanding of the protein interaction
            network of the human liver.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25416956
    review:
      summary: Large-scale human interactome with STAMBP.
      action: ACCEPT
      reason: Large-scale proteomic data supporting protein interactions.
      supported_by:
        - reference_id: PMID:25416956
          supporting_text: A proteome-scale map of the human interactome
            network.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26634441
    review:
      summary: ESCRT-III helical polymer structure showing IST1 binding.
      action: ACCEPT
      reason: Critical structural paper on IST1-CHMP1B copolymers.
      supported_by:
        - reference_id: PMID:26634441
          supporting_text: 2015 Dec 3. Structure and membrane remodeling
            activity of ESCRT-III helical polymers.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:31515488
    review:
      summary: Genetic variants affecting protein interactions with STAMBP.
      action: ACCEPT
      reason: Evidence for CHMP1B-STAMBP interaction.
      supported_by:
        - reference_id: PMID:31515488
          supporting_text: Extensive disruption of protein interactions by
            genetic variants across the allele frequency spectrum in human
            populations.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32296183
    review:
      summary: Binary protein interactome with STAMBP, MITD1, VTA1, PICK1.
      action: ACCEPT
      reason: Large-scale systematic interaction data.
      supported_by:
        - reference_id: PMID:32296183
          supporting_text: Apr 8. A reference map of the human binary protein
            interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: Cell-specific interactome remodeling with CHMP1A and VTA1.
      action: ACCEPT
      reason: Cell-type specific interaction data.
      supported_by:
        - reference_id: PMID:33961781
          supporting_text: 2021 May 6. Dual proteome-scale networks reveal
            cell-specific remodeling of the human interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:40205054
    review:
      summary: Multimodal cell atlas with VTA1 interaction.
      action: ACCEPT
      reason: Large-scale mapping data.
      supported_by:
        - reference_id: PMID:40205054
          supporting_text: Apr 9. Multimodal cell maps as a foundation for
            structural and functional genomics.
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:16730941
    review:
      summary: CHMP1B forms homodimers/oligomers as part of ESCRT-III filament
        assembly.
      action: ACCEPT
      reason: More informative than generic protein binding - documents CHMP1B
        self-interaction for polymerization.
      supported_by:
        - reference_id: PMID:16730941
          supporting_text: 'May 30. A systematic analysis of human CHMP protein interactions:
            additional MIT domain-containing proteins bind to multiple components
            of the human ESCRT III complex.'
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:19525971
    review:
      summary: CHMP1B self-association for filament formation.
      action: ACCEPT
      reason: Structural evidence for CHMP1B homotypic interactions in
        autoinhibited and polymerized states.
      supported_by:
        - reference_id: PMID:19525971
          supporting_text: Jun 14. Structural basis for ESCRT-III protein
            autoinhibition.
  - term:
      id: GO:0000421
      label: autophagosome membrane
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: CHMP1B localizes to autophagosome membranes during autophagy.
      action: ACCEPT
      reason: Direct experimental evidence for localization to autophagosomes.
        Core function in autophagosome maturation.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for
            autophagic clearance of protein aggregates associated with
            neurodegenerative disease.
  - term:
      id: GO:0000776
      label: kinetochore
    evidence_type: IDA
    original_reference_id: PMID:26040712
    review:
      summary: CHMP1B localizes to kinetochores during mitosis.
      action: KEEP_AS_NON_CORE
      reason: Experimental evidence confirms localization but this is a non-core
        mitotic function, not primary ESCRT-III role.
      supported_by:
        - reference_id: PMID:26040712
          supporting_text: Spastin and ESCRT-III coordinate mitotic spindle
            disassembly and nuclear envelope sealing.
  - term:
      id: GO:0000815
      label: ESCRT III complex
    evidence_type: NAS
    original_reference_id: PMID:36107470
    review:
      summary: CHMP1B is a core ESCRT-III component.
      action: ACCEPT
      reason: Fundamental definitional annotation - CHMP1B is by definition an
        ESCRT-III protein.
      supported_by:
        - reference_id: PMID:36107470
          supporting_text: Comprehensive analysis of the human ESCRT-III-MIT
            domain interactome reveals new cofactors for cytokinetic abscission.
  - term:
      id: GO:0001778
      label: plasma membrane repair
    evidence_type: IDA
    original_reference_id: PMID:24482116
    review:
      summary: ESCRT machinery including CHMP1B required for plasma membrane
        repair.
      action: ACCEPT
      reason: Direct experimental demonstration that CHMP1B participates in
        membrane repair via ESCRT-III.
      supported_by:
        - reference_id: PMID:24482116
          supporting_text: 2014 Jan 30. ESCRT machinery is required for plasma
            membrane repair.
  - term:
      id: GO:0005643
      label: nuclear pore
    evidence_type: IDA
    original_reference_id: PMID:26040713
    review:
      summary: CHMP1B localizes to nuclear pore during nuclear envelope
        reformation.
      action: ACCEPT
      reason: Experimental evidence for CHMP1B's role in ESCRT-III-mediated
        nuclear envelope sealing.
      supported_by:
        - reference_id: PMID:26040713
          supporting_text: ESCRT-III controls nuclear envelope reformation.
  - term:
      id: GO:0005765
      label: lysosomal membrane
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: CHMP1B at lysosomal membranes during autophagy and MVB fusion.
      action: ACCEPT
      reason: Direct evidence for lysosomal localization in autophagy context.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for
            autophagic clearance of protein aggregates associated with
            neurodegenerative disease.
  - term:
      id: GO:0005828
      label: kinetochore microtubule
    evidence_type: IDA
    original_reference_id: PMID:26040712
    review:
      summary: Localization to kinetochore microtubules during mitotic spindle
        disassembly.
      action: KEEP_AS_NON_CORE
      reason: Experimental evidence but represents non-core mitotic function.
      supported_by:
        - reference_id: PMID:26040712
          supporting_text: Spastin and ESCRT-III coordinate mitotic spindle
            disassembly and nuclear envelope sealing.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: CHMP1B localizes to plasma membrane during viral budding.
      action: KEEP_AS_NON_CORE
      reason: Valid localization during HIV budding but this is non-core
        function.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their
            relationship to HIV budding.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IMP
    original_reference_id: PMID:17984323
    review:
      summary: CHMP1B required for autophagy via MVB-mediated clearance of
        protein aggregates.
      action: ACCEPT
      reason: Strong experimental evidence that CHMP1B is essential for
        autophagosome maturation.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for
            autophagic clearance of protein aggregates associated with
            neurodegenerative disease.
  - term:
      id: GO:0006997
      label: nucleus organization
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: CHMP1B involved in nuclear organization during and after mitosis.
      action: KEEP_AS_NON_CORE
      reason: Experimental support but broad term covering mitotic roles which
        are non-core.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: Human ESCRT-III and VPS4 proteins are required for
            centrosome and spindle maintenance.
  - term:
      id: GO:0007080
      label: mitotic metaphase chromosome alignment
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: CHMP1B depletion affects chromosome alignment.
      action: KEEP_AS_NON_CORE
      reason: Experimental evidence but represents pleiotropic mitotic defect,
        not core ESCRT function.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: Human ESCRT-III and VPS4 proteins are required for
            centrosome and spindle maintenance.
  - term:
      id: GO:0030496
      label: midbody
    evidence_type: IDA
    original_reference_id: PMID:26040712
    review:
      summary: CHMP1B strongly localizes to midbodies for spastin recruitment
        during cytokinesis.
      action: ACCEPT
      reason: Well-established core localization for cytokinetic abscission
        function.
      supported_by:
        - reference_id: PMID:26040712
          supporting_text: Spastin and ESCRT-III coordinate mitotic spindle
            disassembly and nuclear envelope sealing.
  - term:
      id: GO:0031468
      label: nuclear membrane reassembly
    evidence_type: IMP
    original_reference_id: PMID:26040713
    review:
      summary: CHMP1B required for nuclear envelope reformation via ESCRT-III
        membrane sealing.
      action: ACCEPT
      reason: Strong experimental evidence for essential role in post-mitotic
        nuclear envelope reformation.
      supported_by:
        - reference_id: PMID:26040713
          supporting_text: ESCRT-III controls nuclear envelope reformation.
  - term:
      id: GO:0032585
      label: multivesicular body membrane
    evidence_type: IDA
    original_reference_id: PMID:16554368
    review:
      summary: Core localization to MVB membranes for ILV formation.
      action: ACCEPT
      reason: Direct experimental evidence for central MVB membrane
        localization.
      supported_by:
        - reference_id: PMID:16554368
          supporting_text: Mar 22. The ESCRT-III subunit hVps24 is required for
            degradation but not silencing of the epidermal growth factor
            receptor.
  - term:
      id: GO:0036258
      label: multivesicular body assembly
    evidence_type: NAS
    original_reference_id: PMID:16505166
    review:
      summary: CHMP1B participates in MVB assembly via ESCRT-III polymer
        formation.
      action: ACCEPT
      reason: Core function in MVB biogenesis - fundamental ESCRT-III role.
      supported_by:
        - reference_id: PMID:16505166
          supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is
            regulated by a conserved VSL region in Vta1.
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: CHMP1B contributes to HIV budding but with moderate effect.
      action: KEEP_AS_NON_CORE
      reason: Experimental validation but represents non-core accessory function
        for viral hijacking of ESCRT.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their
            relationship to HIV budding.
  - term:
      id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the
        multivesicular body sorting pathway
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: Core function sorting ubiquitinated cargo for lysosomal
        degradation.
      action: ACCEPT
      reason: Central CHMP1B function with direct experimental support.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for
            autophagic clearance of protein aggregates associated with
            neurodegenerative disease.
  - term:
      id: GO:0046761
      label: viral budding from plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: HIV budding from plasma membrane via ESCRT machinery.
      action: KEEP_AS_NON_CORE
      reason: Experimental evidence but non-core viral hijacking function.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their
            relationship to HIV budding.
  - term:
      id: GO:0051469
      label: vesicle fusion with vacuole
    evidence_type: NAS
    original_reference_id: PMID:16505166
    review:
      summary: Yeast-centric terminology for MVB-lysosome fusion.
      action: MODIFY
      reason: Uses yeast "vacuole" terminology. For mammals should be
        MVB-lysosome fusion (GO:0061763).
      proposed_replacement_terms:
        - id: GO:0061763
          label: multivesicular body-lysosome fusion
      supported_by:
        - reference_id: PMID:16505166
          supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is
            regulated by a conserved VSL region in Vta1.
  - term:
      id: GO:0061763
      label: multivesicular body-lysosome fusion
    evidence_type: NAS
    original_reference_id: PMID:16505166
    review:
      summary: CHMP1B mediates fusion of MVBs with lysosomes for cargo
        degradation.
      action: ACCEPT
      reason: Core function enabling delivery of MVB cargo to lysosomes for
        degradation.
      supported_by:
        - reference_id: PMID:16505166
          supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is
            regulated by a conserved VSL region in Vta1.
  - term:
      id: GO:0061952
      label: midbody abscission
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: CHMP1B essential for cytokinetic abscission via spastin
        recruitment.
      action: ACCEPT
      reason: Well-established core function with strong experimental support.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: Human ESCRT-III and VPS4 proteins are required for
            centrosome and spindle maintenance.
  - term:
      id: GO:0071985
      label: multivesicular body sorting pathway
    evidence_type: IDA
    original_reference_id: PMID:16554368
    review:
      summary: Central pathway for CHMP1B function in cargo sorting.
      action: ACCEPT
      reason: Core CHMP1B pathway - fundamental to its primary function.
      supported_by:
        - reference_id: PMID:16554368
          supporting_text: Mar 22. The ESCRT-III subunit hVps24 is required for
            degradation but not silencing of the epidermal growth factor
            receptor.
  - term:
      id: GO:0090148
      label: membrane fission
    evidence_type: NAS
    original_reference_id: PMID:19234443
    review:
      summary: CHMP1B mediates membrane scission as core ESCRT-III function.
      action: ACCEPT
      reason: Fundamental molecular function of ESCRT-III in driving membrane
        fission events.
      supported_by:
        - reference_id: PMID:19234443
          supporting_text: Membrane scission by the ESCRT-III complex.
  - term:
      id: GO:0097352
      label: autophagosome maturation
    evidence_type: IMP
    original_reference_id: PMID:17984323
    review:
      summary: CHMP1B required for autophagosome-lysosome fusion.
      action: ACCEPT
      reason: Strong experimental evidence for essential role in autophagy.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for
            autophagic clearance of protein aggregates associated with
            neurodegenerative disease.
  - term:
      id: GO:1901673
      label: regulation of mitotic spindle assembly
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: CHMP1B depletion affects spindle assembly.
      action: KEEP_AS_NON_CORE
      reason: Experimental support but represents pleiotropic mitotic effect,
        not core function.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: Human ESCRT-III and VPS4 proteins are required for
            centrosome and spindle maintenance.
  - term:
      id: GO:1902774
      label: late endosome to lysosome transport
    evidence_type: IMP
    original_reference_id: PMID:17984323
    review:
      summary: CHMP1B mediates MVB transport to lysosomes.
      action: ACCEPT
      reason: Core trafficking function with experimental support.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for
            autophagic clearance of protein aggregates associated with
            neurodegenerative disease.
  - term:
      id: GO:1904930
      label: amphisome membrane
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: CHMP1B localizes to amphisome membranes in autophagy.
      action: ACCEPT
      reason: Direct evidence for localization to autophagosome-endosome hybrid
        compartments.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for
            autophagic clearance of protein aggregates associated with
            neurodegenerative disease.
  - term:
      id: GO:0030496
      label: midbody
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: Duplicate midbody localization from immunofluorescence data.
      action: ACCEPT
      reason: Additional experimental support for midbody localization via IF
        imaging.
  - term:
      id: GO:0045184
      label: establishment of protein localization
    evidence_type: IMP
    original_reference_id: PMID:23015756
    review:
      summary: CHMP1B recruits MITD1 to midbodies - establishing protein
        localization.
      action: KEEP_AS_NON_CORE
      reason: Broad term that's technically correct but not informative about
        CHMP1B's specific role.
      supported_by:
        - reference_id: PMID:23015756
          supporting_text: 2012 Sep 26. MITD1 is recruited to midbodies by
            ESCRT-III and participates in cytokinesis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16174732
    review:
      summary: VPS4A MIT domain binding to CHMP1B.
      action: MODIFY
      reason: Paper characterizes MIT-MIM interaction - should use more specific
        MIT domain binding term.
      proposed_replacement_terms:
        - id: GO:0090541
          label: MIT domain binding
      supported_by:
        - reference_id: PMID:16174732
          supporting_text: Structure and ESCRT-III protein interactions of the
            MIT domain of human VPS4A.
  - term:
      id: GO:0090541
      label: MIT domain binding
    evidence_type: IDA
    original_reference_id: PMID:16174732
    review:
      summary: CHMP1B binds MIT domains via its C-terminal MIM motif - critical
        for VPS4 and spastin recruitment.
      action: ACCEPT
      reason: Highly specific and informative molecular function term describing
        key CHMP1B protein-protein interaction mechanism.
      supported_by:
        - reference_id: PMID:16174732
          supporting_text: Structure and ESCRT-III protein interactions of the
            MIT domain of human VPS4A.
  - term:
      id: GO:0036258
      label: multivesicular body assembly
    evidence_type: NAS
    original_reference_id: PMID:20588296
    review:
      summary: Duplicate of earlier annotation - CHMP1B assembles MVBs.
      action: ACCEPT
      reason: Core function, duplicate annotation but consistent.
      supported_by:
        - reference_id: PMID:20588296
          supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:
            it's all in the neck."
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: NAS
    original_reference_id: PMID:20588296
    review:
      summary: Duplicate viral budding annotation.
      action: KEEP_AS_NON_CORE
      reason: Consistent with earlier annotations - non-core viral function.
      supported_by:
        - reference_id: PMID:20588296
          supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:
            it's all in the neck."
  - term:
      id: GO:1904903
      label: ESCRT III complex disassembly
    evidence_type: NAS
    original_reference_id: PMID:20588296
    review:
      summary: CHMP1B participates in VPS4-mediated ESCRT-III disassembly as
        substrate.
      action: ACCEPT
      reason: Important regulatory process - CHMP1B is disassembled by VPS4 to
        recycle ESCRT-III components.
      supported_by:
        - reference_id: PMID:20588296
          supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:
            it's all in the neck."
  - term:
      id: GO:0010008
      label: endosome membrane
    evidence_type: IDA
    original_reference_id: PMID:25556234
    review:
      summary: Endosome membrane localization, likely sorting endosomes for
        IST1-CHMP1B recycling function.
      action: ACCEPT
      reason: Experimental evidence for endosomal membrane localization
        including sorting/early endosomes for IST1-CHMP1B-mediated recycling.
      supported_by:
        - reference_id: PMID:25556234
          supporting_text: 2015 Jan 2. New host factors important for
            respiratory syncytial virus (RSV) replication revealed by a novel
            microfluidics screen for interactors of matrix (M) protein.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18385515
    review:
      summary: VTA1 and LIP5 interactions with CHMP1B.
      action: ACCEPT
      reason: Documents CHMP1B interactions with ESCRT-III regulatory proteins.
      supported_by:
        - reference_id: PMID:18385515
          supporting_text: Apr 2. Novel interactions of ESCRT-III with LIP5 and
            VPS4 and their implications for ESCRT-III disassembly.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23105106
    review:
      summary: LIP5/VTA1 interactions with ESCRT proteins including CHMP1B.
      action: ACCEPT
      reason: Regulatory protein interactions for ESCRT-III function.
      supported_by:
        - reference_id: PMID:23105106
          supporting_text: 2012 Oct 26. Interactions of the human LIP5
            regulatory protein with endosomal sorting complexes required for
            transport.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18997780
    review:
      summary: Critical paper on spastin MIT domain binding to CHMP1B for
        midbody targeting.
      action: MODIFY
      reason: This is the key paper showing spastin-CHMP1B interaction via
        MIT-MIM - should be MIT domain binding.
      proposed_replacement_terms:
        - id: GO:0090541
          label: MIT domain binding
      supported_by:
        - reference_id: PMID:18997780
          supporting_text: 2008 Nov 9. Structural basis for midbody targeting of
            spastin by the ESCRT-III protein CHMP1B.
  - term:
      id: GO:0051301
      label: cell division
    evidence_type: IMP
    original_reference_id: PMID:19129479
    review:
      summary: IST1-CHMP1B function in cytokinesis/cell division.
      action: MODIFY
      reason: Too broad - more specific term is midbody abscission (GO:0061952).
      proposed_replacement_terms:
        - id: GO:0061952
          label: midbody abscission
      supported_by:
        - reference_id: PMID:19129479
          supporting_text: Jan 7. Biochemical analyses of human IST1 and its
            function in cytokinesis.
  - term:
      id: GO:0000815
      label: ESCRT III complex
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: Duplicate ESCRT-III complex membership annotation.
      action: ACCEPT
      reason: Core complex membership - duplicate but consistent.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their
            relationship to HIV budding.
  - term:
      id: GO:0030117
      label: membrane coat
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: ESCRT-III forms helical polymer coats on membranes.
      action: ACCEPT
      reason: Accurate description of CHMP1B filament assembly forming membrane
        coats for constriction and scission.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their
            relationship to HIV budding.
  - term:
      id: GO:0010824
      label: regulation of centrosome duplication
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: CHMP1B depletion affects centrosome duplication.
      action: KEEP_AS_NON_CORE
      reason: Experimental evidence but represents pleiotropic mitotic defect,
        not core ESCRT function.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: Human ESCRT-III and VPS4 proteins are required for
            centrosome and spindle maintenance.
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:23533145
    review:
      summary: HDA annotation from proteomic analysis of exosomes - likely
        contamination.
      action: REMOVE
      reason: HDA (high-throughput direct assay) annotations from exosome
        proteomics often reflect contamination from ESCRT machinery involved in
        exosome biogenesis rather than bona fide exosome components. CHMP1B
        functions inside cells, not as secreted exosome cargo.
      supported_by:
        - reference_id: PMID:23533145
          supporting_text: 2013 Apr 23. In-depth proteomic analyses of exosomes
            isolated from expressed prostatic secretions in urine.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:14519844
    review:
      summary: Early paper on HIV budding showing CHMP1A and VPS4A interactions.
      action: ACCEPT
      reason: Documents key ESCRT-III interactions in viral budding context.
      supported_by:
        - reference_id: PMID:14519844
          supporting_text: Divergent retroviral late-budding domains recruit
            vacuolar protein sorting factors by using alternative adaptor
            proteins.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:14505570
    review:
      summary: Protein network of HIV budding with CHMP1A and VPS4 interactions.
      action: ACCEPT
      reason: Early comprehensive study of ESCRT interactions.
      supported_by:
        - reference_id: PMID:14505570
          supporting_text: The protein network of HIV budding.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23045692
    review:
      summary: MITD1 binding to CHMP1B at midbodies.
      action: ACCEPT
      reason: Documents CHMP1B recruitment of MITD1 for cytokinesis.
      supported_by:
        - reference_id: PMID:23045692
          supporting_text: ESCRT-III binding protein MITD1 is involved in
            cytokinesis and has an unanticipated PLD fold that binds membranes.
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:19056867
    review:
      summary: Urinary exosome proteomics - likely contamination.
      action: REMOVE
      reason: HDA proteomic detection in exosomes likely reflects ESCRT
        machinery contamination, not true exosome localization.
      supported_by:
        - reference_id: PMID:19056867
          supporting_text: 2008 Dec 3. Large-scale proteomics and
            phosphoproteomics of urinary exosomes.
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:20458337
    review:
      summary: B-cell exosome proteomics - likely contamination.
      action: REMOVE
      reason: HDA exosome annotation likely contamination from ESCRT machinery.
      supported_by:
        - reference_id: PMID:20458337
          supporting_text: 2010 May 11. MHC class II-associated proteins in
            B-cell exosomes and potential functional implications for exosome
            biogenesis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21543490
    review:
      summary: ISG15 effects on virus release via VPS4A interaction.
      action: ACCEPT
      reason: Documents VPS4A-CHMP1B interactions in viral budding context.
      supported_by:
        - reference_id: PMID:21543490
          supporting_text: Mechanism of inhibition of retrovirus release from
            cells by interferon-induced gene ISG15.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19129480
    review:
      summary: IST1 interaction with CHMP1B essential for cytokinesis.
      action: ACCEPT
      reason: Critical paper documenting IST1-CHMP1B copolymer formation -
        though generic term, important interaction.
      supported_by:
        - reference_id: PMID:19129480
          supporting_text: Jan 7. Essential role of hIST1 in cytokinesis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19129479
    review:
      summary: Biochemical analyses of IST1-CHMP1B interaction.
      action: ACCEPT
      reason: Key paper on IST1-CHMP1B copolymer function.
      supported_by:
        - reference_id: PMID:19129479
          supporting_text: Jan 7. Biochemical analyses of human IST1 and its
            function in cytokinesis.
  - term:
      id: GO:0019904
      label: protein domain specific binding
    evidence_type: IPI
    original_reference_id: PMID:17928862
    review:
      summary: VPS4 ATPase MIT domain binding to CHMP1B MIM.
      action: MODIFY
      reason: More specific to annotate as MIT domain binding (GO:0090541)
        rather than generic protein domain specific binding.
      proposed_replacement_terms:
        - id: GO:0090541
          label: MIT domain binding
      supported_by:
        - reference_id: PMID:17928862
          supporting_text: ESCRT-III recognition by VPS4 ATPases.
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword
      mapping
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
      Location vocabulary mapping
  - id: GO_REF:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning
      models
  - id: PMID:14505570
    title: The protein network of HIV budding
  - id: PMID:14519844
    title: Divergent retroviral late-budding domains recruit vacuolar protein
      sorting factors by using alternative adaptor proteins
  - id: PMID:16174732
    title: Structure and ESCRT-III protein interactions of the MIT domain of
      human VPS4A
  - id: PMID:16505166
    title: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a
      conserved VSL region in Vta1
  - id: PMID:16554368
    title: The ESCRT-III subunit hVps24 is required for degradation but not
      silencing of the epidermal growth factor receptor
  - id: PMID:16730941
    title: "A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex."
  - id: PMID:17711858
    title: The MIT domain of UBPY constitutes a CHMP binding and endosomal
      localization signal required for efficient epidermal growth factor
      receptor degradation
  - id: PMID:17928862
    title: ESCRT-III recognition by VPS4 ATPases
  - id: PMID:17984323
    title: Functional multivesicular bodies are required for autophagic
      clearance of protein aggregates associated with neurodegenerative disease
  - id: PMID:18385515
    title: Novel interactions of ESCRT-III with LIP5 and VPS4 and their
      implications for ESCRT-III disassembly
  - id: PMID:18997780
    title: Structural basis for midbody targeting of spastin by the ESCRT-III
      protein CHMP1B
  - id: PMID:19056867
    title: Large-scale proteomics and phosphoproteomics of urinary exosomes
  - id: PMID:19129479
    title: Biochemical analyses of human IST1 and its function in cytokinesis
  - id: PMID:19129480
    title: Essential role of hIST1 in cytokinesis
  - id: PMID:19234443
    title: Membrane scission by the ESCRT-III complex
  - id: PMID:19302785
    title: Ab initio protein modelling reveals novel human MIT domains
  - id: PMID:19525971
    title: Structural basis for ESCRT-III protein autoinhibition
  - id: PMID:20458337
    title: MHC class II-associated proteins in B-cell exosomes and potential
      functional implications for exosome biogenesis
  - id: PMID:20588296
    title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.'
  - id: PMID:20616062
    title: Human ESCRT-III and VPS4 proteins are required for centrosome and
      spindle maintenance
  - id: PMID:21543490
    title: Mechanism of inhibition of retrovirus release from cells by
      interferon-induced gene ISG15
  - id: PMID:21827950
    title: Structural basis for ESCRT-III CHMP3 recruitment of AMSH
  - id: PMID:21988832
    title: Toward an understanding of the protein interaction network of the
      human liver
  - id: PMID:23015756
    title: MITD1 is recruited to midbodies by ESCRT-III and participates in
      cytokinesis
  - id: PMID:23045692
    title: ESCRT-III binding protein MITD1 is involved in cytokinesis and has an
      unanticipated PLD fold that binds membranes
  - id: PMID:23105106
    title: Interactions of the human LIP5 regulatory protein with endosomal
      sorting complexes required for transport
  - id: PMID:23533145
    title: In-depth proteomic analyses of exosomes isolated from expressed
      prostatic secretions in urine
  - id: PMID:24482116
    title: ESCRT machinery is required for plasma membrane repair
  - id: PMID:24878737
    title: Structure of cellular ESCRT-III spirals and their relationship to HIV
      budding
  - id: PMID:25416956
    title: A proteome-scale map of the human interactome network
  - id: PMID:25556234
    title: New host factors important for respiratory syncytial virus (RSV)
      replication revealed by a novel microfluidics screen for interactors of
      matrix (M) protein.
  - id: PMID:26040712
    title: Spastin and ESCRT-III coordinate mitotic spindle disassembly and
      nuclear envelope sealing
  - id: PMID:26040713
    title: ESCRT-III controls nuclear envelope reformation
  - id: PMID:26634441
    title: Structure and membrane remodeling activity of ESCRT-III helical
      polymers
  - id: PMID:31515488
    title: Extensive disruption of protein interactions by genetic variants
      across the allele frequency spectrum in human populations
  - id: PMID:32296183
    title: A reference map of the human binary protein interactome
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the
      human interactome
  - id: PMID:36107470
    title: Comprehensive analysis of the human ESCRT-III-MIT domain interactome
      reveals new cofactors for cytokinetic abscission
  - id: PMID:40205054
    title: Multimodal cell maps as a foundation for structural and functional
      genomics
  - id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
    title: Deep research on CHMP1B function and mechanisms
  - id: file:human/CHMP1B/CHMP1B-uniprot.txt
    title: UniProt entry for CHMP1B
core_functions:
  - molecular_function:
      id: GO:0090541
      label: MIT domain binding
    description: CHMP1B binds MIT domains of VPS4 ATPases and spastin via its
      C-terminal MIM motif, with particularly high affinity for spastin (12 μM
      KD) enabling recruitment of spastin to midbodies for cytokinetic
      abscission and VPS4 for ESCRT-III disassembly. This bifunctional binding
      enables context-dependent protein partnerships for diverse membrane
      remodeling processes including MVB formation, endosomal recycling, and
      cytokinesis.
    supported_by:
      - reference_id: file:human/CHMP1B/CHMP1B-uniprot.txt
        supporting_text: Interacts with VPS4A; the interaction is direct.
          Interacts with VPS4B; the interaction is direct. Interacts with SPAST
          (via MIT domain); the interaction is direct
      - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
        supporting_text: The spastin MIT domain recognizes CHMP1B with a
          dissociation constant of approximately 12 μM, approximately 2.75-fold
          higher affinity than VPS4 MIT domain binding. This dual-function
          capacity of the CHMP1B MIM for selective binding to both VPS4 and
          spastin represents a remarkable example of molecular adaptation
  - molecular_function:
      id: GO:0042802
      label: identical protein binding
    description: CHMP1B self-associates to form helical filaments on membranes,
      either as homopolymers or as 1:1 copolymers with IST1. These polymers
      mediate membrane constriction and scission with dual topology specificity
      - reverse-topology for MVB ILV formation and normal-topology for endosomal
      recycling tubule scission.
    supported_by:
      - reference_id: file:human/CHMP1B/CHMP1B-deep-research-perplexity.md
        supporting_text: CHMP1B initially polymerizes into flexible
          single-stranded filaments that wrap around target membranes to induce
          moderate curvature, followed by subsequent IST1 assembly onto CHMP1B
          to progressively constrict the membrane. The two strands interweave
          extensively, with CHMP1B helix α4 binding to multiple segments of the
          IST1 N-terminal domain helix α1, creating a tightly interlocked
          structure

CHMP1B

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

Citations

Perplexity

CHMP1B: Structural Organization, Membrane Remodeling Functions, and Cellular Roles in Protein Sorting and Trafficking

Executive Summary

Protein Structure and ESCRT-III Complex Organization

Structural Architecture and Domain Organization

ESCRT-III Complex Context and Hierarchical Assembly

Molecular Mechanisms in MVB Formation and Membrane Remodeling

Classical Role in MVB Biogenesis and Intraluminal Vesicle Formation

Positive Versus Negative Membrane Curvature Specificity

Cellular Localization and Subcellular Distribution

Endosomal and Vesicular Localization

Midbody Localization During Cytokinesis

Lipid Droplet-Peroxisome Contact Sites

Protein-Protein Interactions and Regulatory Mechanisms

VPS4 Interaction and MIT-MIM Recognition

Spastin MIT Domain Recognition with High Affinity

IST1 Partnership and Copolymer Formation

IST1-CHMP1B Copolymer Formation and Unique Functions

Sequential Polymerization Mechanism and Membrane Constriction

Normal-Topology Membrane Remodeling in Endosomal Recycling

Friction-Driven Membrane Scission Independent of VPS4

Role in Distinct Cellular Processes

HIV-1 Virion Release and Budding

Cytokinetic Abscission and Midbody Dynamics

Endosomal Recycling and Receptor Trafficking

Fatty Acid Trafficking and Lipid Droplet Biology

Regulatory Mechanisms and Post-Translational Modifications

Ubiquitination-Dependent Regulation by USP8

Autoinhibition and Activation Mechanisms

Disease Associations and Clinical Significance

Pontocerebellar Hypoplasia Type 8

Hereditary Spastic Paraplegia Association

Evolutionary Conservation and Structural Insights

Conservation Across Eukaryotic Lineages

Structural Homology to BAR Domain Proteins

Conclusion

Citations

📚 Additional Documentation

Notes

CHMP1B Annotation Review Notes

Gene Overview

Core Functions (from deep research)

Key Evidence

Annotation Review Strategy

Key Papers to Reference

REVIEW COMPLETED - Summary

Summary Statistics

Key Decisions

Core Molecular Functions Identified

Notable Insights

📄 View Raw YAML