Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000813 ESCRT I complex	IBA GO_REF:0000033	ACCEPT	Summary: ESCRT-I complex membership is the central MVB12B cellular-component annotation. Reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Component of the ESCRT-I complex file:human/MVB12B/MVB12B-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12B/MVB12B-uniprot.txt Interacts with TSG101 file:human/MVB12B/MVB12B-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:20654576 MVB12A and MVB12B are subunits of ESCRT-I file:human/MVB12B/MVB12B-deep-research-falcon.md structural component of the ESCRT-I
GO:0005770 late endosome	IBA GO_REF:0000033	ACCEPT	Summary: late endosome localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes
GO:0019075 virus maturation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: virus maturation is directly supported but is a non-core host-pathogen context for this review. Reason: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. Supporting Evidence: PMID:18005716 MVB12 depletion and overexpression inhibit HIV-1 infectivity PMID:18005716 aberrant virion morphologies and altered viral Gag protein processing
GO:0042058 regulation of epidermal growth factor receptor signaling pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: EGF/EGFR pathway context is supported but secondary for MVB12B. Reason: PMID:20654576 links MVB12B post-translational regulation to EGF stimulation and ESCRT-I function, but EGFR regulation is a substrate/context-specific consequence rather than the core function. Supporting Evidence: PMID:20654576 increased upon EGF stimulation PMID:20654576 led to the instability and inclusion of MVB12B
GO:0046755 viral budding	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: viral budding is directly supported but is a non-core host-pathogen context for this review. Reason: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. Supporting Evidence: PMID:18005716 MVB12 depletion and overexpression inhibit HIV-1 infectivity PMID:18005716 aberrant virion morphologies and altered viral Gag protein processing
GO:0005737 cytoplasm	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: cytoplasm is supported as a localization/context row but is not the core MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes
GO:0005768 endosome	IEA GO_REF:0000044	ACCEPT	Summary: endosome localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes
GO:0031902 late endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: late endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Protein binding is too generic to represent MVB12B function. Reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context, not generic protein binding from broad interaction screens. Proposed replacements: ESCRT I complex Supporting Evidence: file:human/MVB12B/MVB12B-notes.md broad localization/context rows but are not the core proteostasis function
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Protein binding is too generic to represent MVB12B function. Reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context, not generic protein binding from broad interaction screens. Proposed replacements: ESCRT I complex Supporting Evidence: file:human/MVB12B/MVB12B-notes.md broad localization/context rows but are not the core proteostasis function
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Protein binding is too generic to represent MVB12B function. Reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context, not generic protein binding from broad interaction screens. Proposed replacements: ESCRT I complex Supporting Evidence: file:human/MVB12B/MVB12B-notes.md broad localization/context rows but are not the core proteostasis function
GO:0046755 viral budding	IMP PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t...	KEEP AS NON CORE	Summary: viral budding is directly supported but is a non-core host-pathogen context for this review. Reason: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. Supporting Evidence: PMID:18005716 MVB12 depletion and overexpression inhibit HIV-1 infectivity PMID:18005716 aberrant virion morphologies and altered viral Gag protein processing
GO:0010008 endosome membrane	TAS Reactome:R-HSA-184269	ACCEPT	Summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes
GO:0010008 endosome membrane	TAS Reactome:R-HSA-3149434	ACCEPT	Summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes
GO:0010008 endosome membrane	TAS Reactome:R-HSA-3159232	ACCEPT	Summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes
GO:0010008 endosome membrane	TAS Reactome:R-HSA-917696	ACCEPT	Summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes
GO:0010008 endosome membrane	TAS Reactome:R-HSA-917730	ACCEPT	Summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes
GO:0019075 virus maturation	IMP PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t...	KEEP AS NON CORE	Summary: virus maturation is directly supported but is a non-core host-pathogen context for this review. Reason: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. Supporting Evidence: PMID:18005716 MVB12 depletion and overexpression inhibit HIV-1 infectivity PMID:18005716 aberrant virion morphologies and altered viral Gag protein processing
GO:0000813 ESCRT I complex	IDA PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t...	ACCEPT	Summary: ESCRT-I complex membership is the central MVB12B cellular-component annotation. Reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Component of the ESCRT-I complex file:human/MVB12B/MVB12B-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12B/MVB12B-uniprot.txt Interacts with TSG101 file:human/MVB12B/MVB12B-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:20654576 MVB12A and MVB12B are subunits of ESCRT-I file:human/MVB12B/MVB12B-deep-research-falcon.md structural component of the ESCRT-I
GO:0000813 ESCRT I complex	IDA PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I...	ACCEPT	Summary: ESCRT-I complex membership is the central MVB12B cellular-component annotation. Reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Component of the ESCRT-I complex file:human/MVB12B/MVB12B-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12B/MVB12B-uniprot.txt Interacts with TSG101 file:human/MVB12B/MVB12B-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:20654576 MVB12A and MVB12B are subunits of ESCRT-I file:human/MVB12B/MVB12B-deep-research-falcon.md structural component of the ESCRT-I
GO:0005515 protein binding	IPI PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I...	MODIFY	Summary: Protein binding should be replaced by ESCRT-I complex membership. Reason: The cited MVB12A/B paper supports ESCRT-I subunit/complex membership rather than a standalone generic protein-binding function. Proposed replacements: ESCRT I complex Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Component of the ESCRT-I complex file:human/MVB12B/MVB12B-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12B/MVB12B-uniprot.txt Interacts with TSG101 file:human/MVB12B/MVB12B-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:20654576 MVB12A and MVB12B are subunits of ESCRT-I file:human/MVB12B/MVB12B-deep-research-falcon.md structural component of the ESCRT-I
GO:0005634 nucleus	IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa...	KEEP AS NON CORE	Summary: nucleus is supported as a localization/context row but is not the core MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes
GO:0005769 early endosome	IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa...	ACCEPT	Summary: early endosome localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes
GO:0005770 late endosome	IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa...	ACCEPT	Summary: late endosome localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes
GO:0005829 cytosol	IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa...	KEEP AS NON CORE	Summary: cytosol is supported as a localization/context row but is not the core MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes
GO:0005886 plasma membrane	IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa...	KEEP AS NON CORE	Summary: plasma membrane is supported as a localization/context row but is not the core MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes
GO:0008289 lipid binding	IMP PMID:22232651 Structural basis for membrane targeting by the MVB12-associa...	MODIFY	Summary: Lipid binding is correct but should be made more specific. Reason: MVB12A/MVB12B MABP domains bind acidic phospholipid-containing liposomes, so phospholipid binding is the more informative MF term. Proposed replacements: phospholipid binding Supporting Evidence: PMID:22232651 MABP domains of the MVB12A and B subunits PMID:22232651 bind in vitro to liposomes containing acidic lipids PMID:22232651 coincidence detector for acidic phospholipids and protein ligands
GO:0031982 vesicle	IDA PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I...	KEEP AS NON CORE	Summary: vesicle is supported as a localization/context row but is not the core MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes
GO:0042058 regulation of epidermal growth factor receptor signaling pathway	IMP PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I...	KEEP AS NON CORE	Summary: EGF/EGFR pathway context is supported but secondary for MVB12B. Reason: PMID:20654576 links MVB12B post-translational regulation to EGF stimulation and ESCRT-I function, but EGFR regulation is a substrate/context-specific consequence rather than the core function. Supporting Evidence: PMID:20654576 increased upon EGF stimulation PMID:20654576 led to the instability and inclusion of MVB12B
GO:0043130 ubiquitin binding	IDA NOT PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I...	ACCEPT	Summary: MVB12B does NOT bind ubiquitin; this is an experimentally-supported negated (NOT) annotation. Reason: This is a curator-made experimental NOT\|enables IDA (negated=true) from PMID:20654576, i.e. the curator established that MVB12B does not directly bind ubiquitin (in ESCRT-I, the TSG101 UEV domain provides ubiquitin binding). The negation is the finding and should be accepted, deferring to the curator's full-text reading rather than left undecided; the cached abstract foregrounds MVB12B ubiquitination, which is a different assay. Supporting Evidence: PMID:20654576 ubiquitination of Lys264 and Lys290 of MVB12B file:human/MVB12B/MVB12B-notes.md The negated ubiquitin-binding row is therefore ACCEPTed as the experimentally-supported non-binding finding
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IC PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I...	ACCEPT	Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of MVB12B/ESCRT-I endosomal cargo sorting. Reason: MVB12B/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Required for the sorting of endocytic file:human/MVB12B/MVB12B-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20654576 sorting of ubiquitinated cargo protein from the plasma membrane to the endosomal vesicle file:human/MVB12B/MVB12B-deep-research-falcon.md MVB12B fulfills an adaptor/scaffold role in recognizing and sorting ubiquitinated membrane proteins into intraluminal vesicles
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: extracellular exosome is supported as a localization/context row but is not the core MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes

Core Functions

MVB12B is a fourth subunit of metazoan ESCRT-I complexes and helps organize MVB12B-containing TSG101-VPS28-VPS37 assemblies for endosomal cargo sorting.

Directly Involved In:

ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

Cellular Locations:

endosome endosome membrane late endosome membrane

In Complex:

ESCRT I complex

Supporting Evidence:

file:human/MVB12B/MVB12B-uniprot.txt
Component of the ESCRT-I complex
file:human/MVB12B/MVB12B-uniprot.txt
which consists of TSG101, VPS28, a VPS37
file:human/MVB12B/MVB12B-uniprot.txt
Interacts with TSG101
file:human/MVB12B/MVB12B-uniprot.txt
Interacts with VPS28
PMID:18005716
constitute the fourth class of metazoan ESCRT-I subunits
PMID:18005716
one copy of each of the four subunit types
PMID:18005716
associate with the core region of the binary TSG101-VPS37 complex
PMID:20654576
MVB12A and MVB12B are subunits of ESCRT-I
file:human/MVB12B/MVB12B-uniprot.txt
Required for the sorting of endocytic
file:human/MVB12B/MVB12B-uniprot.txt
ubiquitinated cargos into multivesicular bodies
PMID:18005716
plays essential roles in HIV budding and endosomal protein sorting
PMID:20654576
sorting of ubiquitinated cargo protein from the plasma membrane to the endosomal vesicle
file:human/MVB12B/MVB12B-uniprot.txt
Endosome
file:human/MVB12B/MVB12B-uniprot.txt
Late endosome membrane
PMID:22232651
function both in protein transport at endosomes

MVB12B MABP-domain acidic phospholipid binding supports ESCRT-I membrane targeting context.

Molecular Function:

phospholipid binding

Directly Involved In:

ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

Cellular Locations:

early endosome late endosome

In Complex:

ESCRT I complex

Supporting Evidence:

PMID:22232651
MABP domains of the MVB12A and B subunits
PMID:22232651
bind in vitro to liposomes containing acidic lipids
PMID:22232651
coincidence detector for acidic phospholipids and protein ligands
file:human/MVB12B/MVB12B-uniprot.txt
Component of the ESCRT-I complex
file:human/MVB12B/MVB12B-uniprot.txt
which consists of TSG101, VPS28, a VPS37
file:human/MVB12B/MVB12B-uniprot.txt
Interacts with TSG101
file:human/MVB12B/MVB12B-uniprot.txt
Interacts with VPS28
PMID:18005716
constitute the fourth class of metazoan ESCRT-I subunits
PMID:18005716
one copy of each of the four subunit types
PMID:18005716
associate with the core region of the binary TSG101-VPS37 complex
PMID:20654576
MVB12A and MVB12B are subunits of ESCRT-I

References

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:18005716

Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding.

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes.

PMID:20654576

Distinct functions of human MVB12A and MVB12B in the ESCRT-I dependent on their posttranslational modifications.

PMID:22232651

Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:33961781

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

Reactome:R-HSA-184269

Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by the ESCRT-I complex

Reactome:R-HSA-3149434

Transport of GAG to the Plasma Membrane

Reactome:R-HSA-3159232

Recruitment Of HIV Virion Budding Machinery

Reactome:R-HSA-917696

Cargo Sequestration

Reactome:R-HSA-917730

Cargo Recognition And Sorting

file:human/MVB12B/MVB12B-uniprot.txt

UniProtKB record for human MVB12B

file:human/MVB12B/MVB12B-notes.md

MVB12B review notes

file:human/MVB12B/MVB12B-deep-research-falcon.md

Falcon deep research report for MVB12B

Suggested Experiments

Experiment: Test purified MVB12B MABP/UMA regions for acidic phospholipid binding and ubiquitin binding using matched mutants, then measure rescue in endosomal cargo-sorting assays.

Hypothesis: MVB12B membrane recognition is better represented by phospholipid binding than generic protein binding, while ubiquitin binding requires direct confirmation.

Type: MVB12B molecular-function refinement

Experiment: Compare MVB12A and MVB12B knockout/rescue in EGFR degradation, ESCRT-I recruitment, and HIV budding assays under matched expression conditions.

Hypothesis: MVB12A and MVB12B differ in endosomal cargo-sorting and EGF-stimulated post-translational regulation.

Type: MVB12 paralog ESCRT-I sorting comparison

Deep Research

Falcon

(MVB12B-deep-research-falcon.md)

Research Report: Functional Annotation of Human MVB12B (UniProt: Q9H7P6) Falcon Edison Scientific Literature 30 citations 2 artifacts 2026-06-20T06:49:29.253492

Edison artifact artifact-00 (text/markdown)

Edison artifact artifact-01 (text/markdown)

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 Report: Functional Annotation of Human MVB12B (UniProt: Q9H7P6)

1. Key Concepts and Definitions

MVB12B (Multivesicular body subunit 12B, also known as FAM125B, C9orf28) is a cytosolic protein in Homo sapiens and a structural component of the ESCRT-I (Endosomal Sorting Complex Required for Transport-I) complex (morita2007identificationofhuman pages 1-2, flower2020ahelicalassembly pages 1-2, morita2007identificationofhuman pages 3-5). As the fourth subunit within the core ESCRT-I heterotetramer (the others are TSG101, VPS28, VPS37), MVB12B fulfills an adaptor/scaffold role in recognizing and sorting ubiquitinated membrane proteins into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs), a critical process for endosomal trafficking, lysosome targeting, and exosome secretion (vietri2020themanyfunctions pages 1-2, morita2007identificationofhuman pages 5-6, kuchitsu2023stingsignallingis pages 1-2).

MVB12B encompasses two key domains:
- MABP domain, implicated in membrane interactions and trafficking.
- UMA (UBAP1-MVB12-associated) domain, essential for ESCRT-I integration and cargo recognition (souza2010umaandmabp pages 1-2).

The protein is not an enzyme and does not possess substrate specificity in the classical sense; its molecular role is instead structural and regulatory within the ESCRT-I assembly (morita2007identificationofhuman pages 1-2, vietri2020themanyfunctions pages 1-2).

2. Recent Developments and Latest Research (2023–2024 priority)

Recent reviews (2023–2024) of the ESCRT system confirm MVB12B’s importance in:
- Endosomal trafficking, MVB/exosome biogenesis, and reverse-topology membrane remodeling events such as virus budding, autophagosome closure, and cytokinesis (vietri2020themanyfunctions pages 1-2, vietri2020themanyfunctions pages 2-3, vietri2020themanyfunctions pages 3-4).
- Immune regulation: Landmark studies reveal that TBK1-dependent phosphorylation of MVB12B is a critical trigger for sorting cytosolic DNA into extracellular vesicles via ESCRT-I, enabling paracrine cGAS–STING signaling during bacterial infection (kuchitsu2023stingsignallingis pages 1-2, nandakumar2019intracellularbacteriaengage pages 1-5, nandakumar2019intracellularbacteriaengage pages 5-15).
- Viral egress: New structural biology work (Flower et al. 2020) details the helical organization of human ESCRT-I and the essential scaffolding role of MVB12B and relatives in membrane remodeling, especially at viral assembly sites (flower2020ahelicalassembly pages 1-2).

3. Cellular Localization and Function

MVB12B is primarily cytosolic, becoming transiently and specifically recruited to endosomal and multivesicular body (MVB) membranes during ILV biogenesis. It localizes to early and late endosomes and MVBs, where it participates in complex assembly, cargo recognition, and vesicle scission (vietri2020themanyfunctions pages 1-2, morita2007identificationofhuman pages 1-2, morita2007identificationofhuman pages 3-5).

Within the ESCRT-I complex, MVB12B interacts with TSG101 and VPS37 (via conserved C-terminal elements), forming a 1:1:1:1 heterotetrameric assembly that binds upstream factors and mediates downstream ESCRT-II/III recruitment for membrane budding and scission (flower2020ahelicalassembly pages 1-2, flower2020ahelicalassembly pages 3-4, souza2010umaandmabp pages 1-2, morita2007identificationofhuman pages 5-6).

4. Biological Pathways and Real-world Relevance

Multivesicular Body Biogenesis & Exosome Formation

Essential for sorting ubiquitinated cargoes into MVBs and regulating the fate of membrane proteins toward the lysosome or exosomal secretion (vietri2020themanyfunctions pages 1-2, kuchitsu2023stingsignallingis pages 1-2).

Viral Budding & Pathogen Interaction

MVB12B-containing ESCRT-I is required for virus budding in HIV-1 and other enveloped viruses, acting as a critical host factor in viral particle release and membrane scission (morita2007identificationofhuman pages 1-2, morita2007identificationofhuman pages 5-6).

Immune Pathways (STING–TBK1–MVB12B Axis)

Upon cytosolic DNA detection (during infection), TBK1 phosphorylates MVB12B (notably at S222), enabling the sorting of immunostimulatory DNA into extracellular vesicles/exosomes to activate cGAS–STING signaling in bystander (uninfected) cells, and promoting type I interferon responses (kuchitsu2023stingsignallingis pages 1-2, nandakumar2019intracellularbacteriaengage pages 1-5, nandakumar2019intracellularbacteriaengage pages 5-15).

Cell Division and Membrane Repair

ESCRT-I (and thus MVB12B) is recruited to the midbody during the terminal stage of cytokinesis to mediate abscission. It is also involved in membrane repair following physical or pathogen-induced membrane damage (vietri2020themanyfunctions pages 1-2, vietri2020themanyfunctions pages 2-3, vietri2020themanyfunctions pages 3-4).

Autophagy and Lysosomal Trafficking

ESCRT-I, with MVB12B, is reliably implicated in the closure of autophagosomes and targeting cargoes for lysosomal degradation (vietri2020themanyfunctions pages 1-2, kuchitsu2023stingsignallingis pages 1-2).

5. Expert Opinions, Analyses, and Relevant Data

Functional specificity: MVB12B’s role as an ESCRT-I subunit is distinguished from yeast Mvb12 by unique metazoan domains and functional regulation via phosphorylation.
Complex stoichiometry: Biophysical studies confirm ESCRT-I containing MVB12B forms a stoichiometric 1:1:1:1 complex with core partners in solution and in vivo (flower2020ahelicalassembly pages 1-2, morita2007identificationofhuman pages 5-6).
Experimental loss-of-function and mutagenesis: Knockdown or mutation of MVB12B impairs HIV-1 release, abnormalizes Gag processing, and blocks EV-mediated paracrine signaling in STING pathway activation, demonstrating strong biological specificity and necessity (nandakumar2019intracellularbacteriaengage pages 5-15, morita2007identificationofhuman pages 1-2).
Imaging and biochemical evidence: Co-localization, size-exclusion chromatography, and electron microscopy provide consistent evidence for subcellular targeting and complex assembly of MVB12B (vietri2020themanyfunctions pages 1-2, kuchitsu2023stingsignallingis pages 1-2).

6. Structured Summaries

The following tables summarize, respectively, the protein features of MVB12B and its roles in key cellular pathways, with direct citation mapping:

Feature	Summary	Evidence/Citation
Approved identity	Human MVB12B protein corresponding to UniProt Q9H7P6; also called FAM125B and C9orf28	Primary literature identifies human MVB12B/FAM125B as an ESCRT-I subunit and distinguishes it from the related paralog MVB12A (morita2007identificationofhuman pages 1-2, morita2007identificationofhuman pages 3-5)
Protein family	Member of the MVB12 family, one of the metazoan fourth-subunit classes of ESCRT-I	Human ESCRT-I contains TSG101, VPS28, VPS37, and a fourth subunit such as MVB12A/MVB12B; UMA-containing proteins are the metazoan MVB12-type subunits (flower2020ahelicalassembly pages 1-2, vietri2020themanyfunctions pages 1-2, souza2010umaandmabp pages 1-2)
Main molecular role	Structural/adaptor subunit of ESCRT-I involved in endosomal cargo sorting and reverse-topology membrane remodeling rather than enzymatic catalysis	ESCRT-I is an upstream complex in multivesicular body biogenesis and other membrane scission events; MVB12 proteins constitute the fourth ESCRT-I subunit class (morita2007identificationofhuman pages 1-2, vietri2020themanyfunctions pages 1-2)
Core binding partners	Directly associates with TSG101 and VPS37 within the ESCRT-I core; assembled complex also includes VPS28	Mapping experiments showed MVB12 proteins bind the TSG101–VPS37 binary complex, and quaternary complexes contain TSG101, VPS28, VPS37, and MVB12 (morita2007identificationofhuman pages 3-5, morita2007identificationofhuman pages 5-6)
Binding architecture	MVB12-family proteins incorporate into the ESCRT-I head/core through the UMA region; human MVB12A structure indicates analogous occupancy of the MVB12 site in human ESCRT-I	Structural work showed UMA-containing human MVB12 proteins integrate into ESCRT-I despite divergence from yeast Mvb12; human ESCRT-I head includes TSG101–VPS28–VPS37B–MVB12A, supporting conserved family organization relevant to MVB12B (flower2020ahelicalassembly pages 1-2, flower2020ahelicalassembly pages 3-4, souza2010umaandmabp pages 1-2)
Key domains	Contains UMA and MABP domains; these domains are implicated in ESCRT-I association and membrane-related trafficking functions	Domain analysis of human MVB12A/B identified UMA and MABP as characteristic features of metazoan MVB12 proteins (souza2010umaandmabp pages 1-2)
Complex stoichiometry	ESCRT-I forms a 1:1:1:1 heterotetramer of TSG101:VPS28:VPS37:MVB12	Hydrodynamic and sedimentation analyses showed soluble human ESCRT-I complexes contain one copy of each subunit type; recombinant complex mass matched a monomeric 1:1:1:1 assembly (morita2007identificationofhuman pages 1-2, morita2007identificationofhuman pages 5-6)
Subcellular localization	Predominantly a cytosolic/endosomal trafficking factor that is transiently recruited to endosomal membranes, especially sites of multivesicular body (MVB) / intraluminal vesicle (ILV) formation	ESCRT-I is distributed in cytoplasm at steady state but is recruited to membranes during MVB vesicle formation; ESCRT-I functions in endosomal cargo sorting and ILV biogenesis (morita2007identificationofhuman pages 1-2, vietri2020themanyfunctions pages 1-2)
Functional cellular compartment	Acts mainly at early/late endosomal membranes and MVBs where ubiquitinated cargo is sorted toward lysosomal degradation or exosome release	Reviews describe ESCRT-I as a bridge between cargo-recognition systems and downstream ESCRT machinery during MVB biogenesis and exosome-related pathways (vietri2020themanyfunctions pages 1-2, kuchitsu2023stingsignallingis pages 1-2)
Post-translational regulation	TBK1-dependent phosphorylation of MVB12B, including S222, regulates its immune-related EV sorting function	In bacterial infection/DNA-stimulation models, MVB12b was identified as a TBK1 phosphotarget, and the S222A mutant impaired the EV-mediated bystander IFN response (nandakumar2019intracellularbacteriaengage pages 1-5, nandakumar2019intracellularbacteriaengage pages 5-15)
Specialized regulated function	Phosphorylated MVB12B helps sort DNA into extracellular vesicles/exosomes for paracrine cGAS–STING signaling	MVB12b deficiency or mutation disrupted transfer of IFN-inducing material in EVs from infected or DNA-stimulated donor cells (nandakumar2019intracellularbacteriaengage pages 1-5, nandakumar2019intracellularbacteriaengage pages 5-15)
Relationship to broader ESCRT functions	Through ESCRT-I, MVB12B contributes to MVB biogenesis, exosome production, viral budding, cytokinetic abscission, autophagy-linked membrane events, and membrane repair	ESCRT-I is a core upstream module reused across multiple reverse-topology membrane remodeling pathways (vietri2020themanyfunctions pages 1-2, vietri2020themanyfunctions pages 2-3, vietri2020themanyfunctions pages 3-4)

Table: This table summarizes the verified identity, molecular role, domain architecture, binding partners, localization, stoichiometry, and regulatory phosphorylation of human MVB12B. It is useful as a concise evidence-based reference for functional annotation of Q9H7P6.

Biological process / pathway	Specific role of MVB12B / ESCRT-I	Key evidence / mechanistic note	Citations
Multivesicular body (MVB) biogenesis and intraluminal vesicle (ILV) formation	MVB12B is a fourth subunit of human ESCRT-I, which acts upstream of ESCRT-II/III during endosomal cargo sorting and ILV formation in MVBs.	Human ESCRT-I is a 1:1:1:1 heterotetramer containing TSG101, VPS28, VPS37 and an MVB12-family subunit; ESCRT-I is recruited to endosomal membranes and helps organize downstream ESCRT assembly for reverse-topology membrane budding.	(flower2020ahelicalassembly pages 1-2, morita2007identificationofhuman pages 1-2, vietri2020themanyfunctions pages 1-2, morita2007identificationofhuman pages 5-6)
Exosome biogenesis and secretion	Through its role in ESCRT-I, MVB12B contributes to formation of ILVs within MVBs that can later be secreted as exosomes when MVBs fuse with the plasma membrane.	Reviews of ESCRT-dependent exosome biogenesis place ESCRT-I as a core organizer of ILV generation and exosome production; MVB12-family proteins are part of this machinery in metazoans.	(vietri2020themanyfunctions pages 1-2, kuchitsu2023stingsignallingis pages 1-2)
Viral budding and egress (HIV-1)	MVB12B supports ESCRT-I function in HIV-1 budding; perturbing MVB12 proteins disrupts virion release and causes abnormal viral assembly and Gag processing.	Foundational work identified human MVB12 proteins as ESCRT-I subunits required for efficient HIV budding, linking MVB12B directly to viral membrane scission.	(morita2007identificationofhuman pages 1-2, morita2007identificationofhuman pages 5-6)
Viral budding and egress (broader ESCRT-dependent viruses)	MVB12B is inferred to contribute when viruses hijack ESCRT-I for budding or egress, because ESCRT-I is a recurrent viral cofactor across enveloped viruses.	Recent reviews emphasize ESCRT-I as a host module used in enveloped virus release; MVB12-family subunits are part of the human ESCRT-I complex that can be co-opted in these contexts.	(flower2020ahelicalassembly pages 1-2, vietri2020themanyfunctions pages 1-2)
Innate immune signaling (STING-TBK1-MVB12B axis)	MVB12B is phosphorylated downstream of STING-TBK1 signaling and mediates extracellular-vesicle-based paracrine immune communication.	During intracellular bacterial infection, TBK1-dependent phosphorylation of MVB12B is required for packaging immunostimulatory DNA into extracellular vesicles, enabling bystander cGAS-STING activation.	(nandakumar2019intracellularbacteriaengage pages 1-5, nandakumar2019intracellularbacteriaengage pages 5-15)
DNA sorting into extracellular vesicles	MVB12B has a specialized cargo-selection role in sorting DNA into EVs/exosomes, beyond a purely structural ESCRT-I function.	Mvb12b knockout or mutation of the TBK1-regulated phosphorylation site impairs EV-mediated DNA transfer and downstream IFN induction in recipient cells.	(nandakumar2019intracellularbacteriaengage pages 1-5, nandakumar2019intracellularbacteriaengage pages 5-15)
Cytokinesis and abscission	MVB12B is not individually singled out in the cited cytokinesis reviews, but as an ESCRT-I subunit it is part of the upstream ESCRT-I module that helps recruit/organize downstream ESCRT-III during abscission.	ESCRT-I is positioned at the top of the abscission pathway, where TSG101 and associated ESCRT-I proteins help nucleate ESCRT-II/III assembly at the midbody.	(vietri2020themanyfunctions pages 1-2, vietri2020themanyfunctions pages 2-3, vietri2020themanyfunctions pages 3-4)
Autophagy and lysosomal trafficking	MVB12B likely participates in ESCRT-I-dependent membrane remodeling steps linked to autophagosome closure, endolysosomal trafficking, and cargo delivery to lysosomes.	ESCRT reviews describe ESCRT-I as part of the upstream machinery in autophagy-related and lysosomal trafficking pathways, although the evidence is generally at complex level rather than MVB12B-specific.	(flower2020ahelicalassembly pages 1-2, vietri2020themanyfunctions pages 1-2, kuchitsu2023stingsignallingis pages 1-2)
Membrane repair	MVB12B is plausibly involved as an ESCRT-I component in membrane repair pathways that depend on coordinated ESCRT recruitment and remodeling.	Reviews describe ESCRT machinery in membrane sealing/repair; the clearest direct mechanistic assignments are often to ESCRT-III/VPS4, with ESCRT-I acting upstream in recruitment/scaffolding.	(vietri2020themanyfunctions pages 1-2, vietri2020themanyfunctions pages 2-3, vietri2020themanyfunctions pages 3-4)

Table: This table summarizes the main biological processes linked to human MVB12B as an ESCRT-I subunit, highlighting where evidence is direct for MVB12B versus inferred from ESCRT-I complex biology. It is useful for separating well-supported specialized roles, such as TBK1-dependent DNA sorting into EVs, from broader complex-level functions like cytokinesis and membrane repair.

7. Citation List, URLs, and Publication Dates (Selection)

Flower TG et al., Nature Structural & Molecular Biology, 2020. https://doi.org/10.1038/s41594-020-0426-4 (Structure/function)
Morita E et al., Cell Host & Microbe, 2007. https://doi.org/10.1016/j.chom.2007.06.003 (ESCRT-I subunit identification)
Nandakumar R et al., Nature Microbiology, 2019. https://doi.org/10.1038/s41564-019-0367-z (TBK1/MVB12B immune pathway)
Kuchitsu Y et al., Nature Cell Biology, 2023. https://doi.org/10.1038/s41556-023-01098-9 (STING/MVB12B/ESCRT in immunity)
Vietri M et al., Nature Reviews Molecular Cell Biology, 2020. https://doi.org/10.1038/s41580-019-0177-4 (ESCRT system overview)
de Souza RF et al., Bioinformatics, 2010. https://doi.org/10.1093/bioinformatics/btq235 (Domain analysis)

8. Conclusion

MVB12B (Q9H7P6) is a canonical human ESCRT-I subunit with central roles in membrane trafficking, exosome/ILV biogenesis, pathogen interaction, and immune regulation. The latest research (2023–2024) highlights its phosphorylation-dependent control of immune vesicle sorting and conserved structural contribution to ESCRT-I function in a variety of essential biological contexts.

This evidence-based functional annotation should serve as a robust and up-to-date resource for research utilizing the human MVB12B gene and protein.

References

(morita2007identificationofhuman pages 1-2): Eiji Morita, Virginie Sandrin, Steven L. Alam, Debra M. Eckert, Steven P. Gygi, and Wesley I. Sundquist. Identification of human mvb12 proteins as escrt-i subunits that function in hiv budding. Cell host & microbe, 2 1:41-53, Jul 2007. URL: https://doi.org/10.1016/j.chom.2007.06.003, doi:10.1016/j.chom.2007.06.003. This article has 174 citations and is from a highest quality peer-reviewed journal.
(flower2020ahelicalassembly pages 1-2): Thomas G. Flower, Yoshinori Takahashi, Arpa Hudait, Kevin Rose, Nicholas Tjahjono, Alexander J. Pak, Adam L. Yokom, Xinwen Liang, Hong-Gang Wang, Fadila Bouamr, Gregory A. Voth, and James H. Hurley. A helical assembly of human escrt-i scaffolds reverse-topology membrane scission. Nature Structural & Molecular Biology, 27:570-580, May 2020. URL: https://doi.org/10.1038/s41594-020-0426-4, doi:10.1038/s41594-020-0426-4. This article has 75 citations and is from a highest quality peer-reviewed journal.
(morita2007identificationofhuman pages 3-5): Eiji Morita, Virginie Sandrin, Steven L. Alam, Debra M. Eckert, Steven P. Gygi, and Wesley I. Sundquist. Identification of human mvb12 proteins as escrt-i subunits that function in hiv budding. Cell host & microbe, 2 1:41-53, Jul 2007. URL: https://doi.org/10.1016/j.chom.2007.06.003, doi:10.1016/j.chom.2007.06.003. This article has 174 citations and is from a highest quality peer-reviewed journal.
(vietri2020themanyfunctions pages 1-2): Marina Vietri, Maja Radulovic, and Harald Stenmark. The many functions of escrts. Nature Reviews Molecular Cell Biology, 21:25-42, Nov 2020. URL: https://doi.org/10.1038/s41580-019-0177-4, doi:10.1038/s41580-019-0177-4. This article has 1079 citations and is from a domain leading peer-reviewed journal.
(morita2007identificationofhuman pages 5-6): Eiji Morita, Virginie Sandrin, Steven L. Alam, Debra M. Eckert, Steven P. Gygi, and Wesley I. Sundquist. Identification of human mvb12 proteins as escrt-i subunits that function in hiv budding. Cell host & microbe, 2 1:41-53, Jul 2007. URL: https://doi.org/10.1016/j.chom.2007.06.003, doi:10.1016/j.chom.2007.06.003. This article has 174 citations and is from a highest quality peer-reviewed journal.
(kuchitsu2023stingsignallingis pages 1-2): Yoshihiko Kuchitsu, Kojiro Mukai, Rei Uematsu, Yuki Takaada, Ayumi Shinojima, Ruri Shindo, Tsumugi Shoji, Shiori Hamano, Emari Ogawa, Ryota Sato, Kensuke Miyake, Akihisa Kato, Yasushi Kawaguchi, Masahiko Nishitani-Isa, Kazushi Izawa, Ryuta Nishikomori, Takahiro Yasumi, Takehiro Suzuki, Naoshi Dohmae, Takefumi Uemura, Glen N. Barber, Hiroyuki Arai, Satoshi Waguri, and Tomohiko Taguchi. Sting signalling is terminated through escrt-dependent microautophagy of vesicles originating from recycling endosomes. Nature Cell Biology, 25:453-466, Mar 2023. URL: https://doi.org/10.1038/s41556-023-01098-9, doi:10.1038/s41556-023-01098-9. This article has 204 citations and is from a highest quality peer-reviewed journal.
(souza2010umaandmabp pages 1-2): Robson F De Souza, L. Aravind, and Alex Bateman. Uma and mabp domains throw light on receptor endocytosis and selection of endosomal cargoes. Bioinformatics, 26:1477-1480, May 2010. URL: https://doi.org/10.1093/bioinformatics/btq235, doi:10.1093/bioinformatics/btq235. This article has 37 citations and is from a highest quality peer-reviewed journal.
(vietri2020themanyfunctions pages 2-3): Marina Vietri, Maja Radulovic, and Harald Stenmark. The many functions of escrts. Nature Reviews Molecular Cell Biology, 21:25-42, Nov 2020. URL: https://doi.org/10.1038/s41580-019-0177-4, doi:10.1038/s41580-019-0177-4. This article has 1079 citations and is from a domain leading peer-reviewed journal.
(vietri2020themanyfunctions pages 3-4): Marina Vietri, Maja Radulovic, and Harald Stenmark. The many functions of escrts. Nature Reviews Molecular Cell Biology, 21:25-42, Nov 2020. URL: https://doi.org/10.1038/s41580-019-0177-4, doi:10.1038/s41580-019-0177-4. This article has 1079 citations and is from a domain leading peer-reviewed journal.
(nandakumar2019intracellularbacteriaengage pages 1-5): Ramya Nandakumar, Roland Tschismarov, Felix Meissner, Thaneas Prabakaran, Abhichart Krissanaprasit, Ensieh Farahani, Bao-cun Zhang, Sonia Assil, Amandine Martin, Wilhelm Bertrams, Christian K. Holm, Andrea Ablasser, Tanja Klause, Martin K. Thomsen, Bernd Schmeck, Kenneth A. Howard, Thomas Henry, Kurt V. Gothelf, Thomas Decker, and Søren R. Paludan. Intracellular bacteria engage a sting–tbk1–mvb12b pathway to enable paracrine cgas–sting signalling. Feb 2019. URL: https://doi.org/10.1038/s41564-019-0367-z, doi:10.1038/s41564-019-0367-z. This article has 144 citations and is from a highest quality peer-reviewed journal.
(nandakumar2019intracellularbacteriaengage pages 5-15): Ramya Nandakumar, Roland Tschismarov, Felix Meissner, Thaneas Prabakaran, Abhichart Krissanaprasit, Ensieh Farahani, Bao-cun Zhang, Sonia Assil, Amandine Martin, Wilhelm Bertrams, Christian K. Holm, Andrea Ablasser, Tanja Klause, Martin K. Thomsen, Bernd Schmeck, Kenneth A. Howard, Thomas Henry, Kurt V. Gothelf, Thomas Decker, and Søren R. Paludan. Intracellular bacteria engage a sting–tbk1–mvb12b pathway to enable paracrine cgas–sting signalling. Feb 2019. URL: https://doi.org/10.1038/s41564-019-0367-z, doi:10.1038/s41564-019-0367-z. This article has 144 citations and is from a highest quality peer-reviewed journal.
(flower2020ahelicalassembly pages 3-4): Thomas G. Flower, Yoshinori Takahashi, Arpa Hudait, Kevin Rose, Nicholas Tjahjono, Alexander J. Pak, Adam L. Yokom, Xinwen Liang, Hong-Gang Wang, Fadila Bouamr, Gregory A. Voth, and James H. Hurley. A helical assembly of human escrt-i scaffolds reverse-topology membrane scission. Nature Structural & Molecular Biology, 27:570-580, May 2020. URL: https://doi.org/10.1038/s41594-020-0426-4, doi:10.1038/s41594-020-0426-4. This article has 75 citations and is from a highest quality peer-reviewed journal.

Artifacts

Citations

souza2010umaandmabp pages 1-2
flower2020ahelicalassembly pages 1-2
morita2007identificationofhuman pages 1-2
morita2007identificationofhuman pages 3-5
vietri2020themanyfunctions pages 1-2
morita2007identificationofhuman pages 5-6
kuchitsu2023stingsignallingis pages 1-2
vietri2020themanyfunctions pages 2-3
vietri2020themanyfunctions pages 3-4
nandakumar2019intracellularbacteriaengage pages 1-5
nandakumar2019intracellularbacteriaengage pages 5-15
flower2020ahelicalassembly pages 3-4
https://doi.org/10.1038/s41594-020-0426-4
https://doi.org/10.1016/j.chom.2007.06.003
https://doi.org/10.1038/s41564-019-0367-z
https://doi.org/10.1038/s41556-023-01098-9
https://doi.org/10.1038/s41580-019-0177-4
https://doi.org/10.1093/bioinformatics/btq235
https://doi.org/10.1038/s41594-020-0426-4](https://doi.org/10.1038/s41594-020-0426-4
https://doi.org/10.1016/j.chom.2007.06.003](https://doi.org/10.1016/j.chom.2007.06.003
https://doi.org/10.1038/s41564-019-0367-z](https://doi.org/10.1038/s41564-019-0367-z
https://doi.org/10.1038/s41556-023-01098-9](https://doi.org/10.1038/s41556-023-01098-9
https://doi.org/10.1038/s41580-019-0177-4](https://doi.org/10.1038/s41580-019-0177-4
https://doi.org/10.1093/bioinformatics/btq235](https://doi.org/10.1093/bioinformatics/btq235
https://doi.org/10.1016/j.chom.2007.06.003,
https://doi.org/10.1038/s41594-020-0426-4,
https://doi.org/10.1038/s41580-019-0177-4,
https://doi.org/10.1038/s41556-023-01098-9,
https://doi.org/10.1093/bioinformatics/btq235,
https://doi.org/10.1038/s41564-019-0367-z,

📚 Additional Documentation

Notes

(MVB12B-notes.md)

MVB12B review notes

Scope

MVB12B is reviewed in the PN ESCRT-I branch. PN entries without PMIDs were used as context only. MVB12B is a metazoan fourth subunit of ESCRT-I, closely related to MVB12A, with direct ESCRT-I and HIV-budding evidence from the MVB12 paper and direct MABP-domain lipid-binding evidence. Viral budding and virus maturation are supported but non-core contexts for this proteostasis review.

Evidence synthesis

MVB12B is a metazoan ESCRT-I fourth subunit. UniProt describes it as a "Component of the ESCRT-I complex" and says it is "Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies" [file:human/MVB12B/MVB12B-uniprot.txt, "Component of the ESCRT-I complex"; file:human/MVB12B/MVB12B-uniprot.txt, "Required for the sorting of endocytic"]. UniProt also states that ESCRT-I "consists of TSG101, VPS28, a VPS37 protein" plus MVB12A or MVB12B, and that MVB12B interacts with TSG101, VPS28, VPS37B, and VPS37C [file:human/MVB12B/MVB12B-uniprot.txt, "which consists of TSG101, VPS28, a VPS37"; file:human/MVB12B/MVB12B-uniprot.txt, "Interacts with TSG101"; file:human/MVB12B/MVB12B-uniprot.txt, "Interacts with VPS28"; file:human/MVB12B/MVB12B-uniprot.txt, "Interacts with VPS37B"].

The main ESCRT-I/MVB12 paper directly supports MVB12B as an ESCRT-I subunit and viral-budding regulator. It reports that MVB12A and MVB12B "constitute the fourth class of metazoan ESCRT-I subunits", that soluble human ESCRT-I complexes contain one copy of each subunit type, and that MVB12 subunits associate with the TSG101-VPS37 core [PMID:18005716, "constitute the fourth class of metazoan ESCRT-I subunits"; PMID:18005716, "one copy of each of the four subunit types"; PMID:18005716, "associate with the core region of the binary TSG101-VPS37 complex"]. The same abstract says MVB12 depletion or overexpression inhibits HIV-1 infectivity and causes viral assembly defects [PMID:18005716, "MVB12 depletion and overexpression inhibit HIV-1 infectivity"; PMID:18005716, "aberrant virion morphologies and altered viral Gag protein processing"]. This supports viral budding/virus maturation as real but non-core host-pathogen contexts.

MVB12B has MABP-domain lipid-binding evidence. The MABP structural paper reports that MVB12A and MVB12B MABP domains bind acidic-lipid liposomes in vitro, that the MABP domain can autonomously localize to puncta and plasma membrane, and that ESCRT-I can act as a detector for acidic phospholipids and protein ligands [PMID:22232651, "MABP domains of the MVB12A and B subunits"; PMID:22232651, "bind in vitro to liposomes containing acidic lipids"; PMID:22232651, "coincidence detector for acidic phospholipids and protein ligands"]. This argues that broad lipid binding should be modified to phospholipid binding (GO:0005543).

PMID:20654576 compares post-translational regulation of MVB12A and MVB12B in ESCRT-I. Its abstract says MVB12B is ubiquitinated at Lys264 and Lys290, that these ubiquitinations increase after EGF stimulation, and that this regulates MVB12B stability and inclusion formation [PMID:20654576, "ubiquitination of Lys264 and Lys290 of MVB12B"; PMID:20654576, "increased upon EGF stimulation"; PMID:20654576, "led to the instability and inclusion of MVB12B"]. This supports EGF/ESCRT-I context and MVB12B post-translational regulation (MVB12B is itself ubiquitinated), which is a different assay from ubiquitin binding. The relevant GOA GO:0043130 ubiquitin binding row is a negated (NOT|enables) IDA: the curator experimentally established that MVB12B does not directly bind ubiquitin (in ESCRT-I, ubiquitin binding is provided by the TSG101 UEV domain). The negated ubiquitin-binding row is therefore ACCEPTed as the experimentally-supported non-binding finding, deferring to the curator's full-text reading.

Nucleus, cytosol/cytoplasm, plasma membrane, vesicle, and extracellular exosome rows are supported localization/context rows but are not the core proteostasis function. The core function remains ESCRT-I-dependent endosomal sorting of ubiquitinated cargo and associated acidic-phospholipid membrane recognition.

Falcon

Falcon deep research was started for MVB12B on 2026-06-02 but timed out after 600 seconds and did not produce a usable MVB12B-deep-research-falcon.md report. The review therefore relies on the local UniProt, GOA, cached-publication, Reactome, and PN-context evidence summarized above.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

Moved out of the YAML description: viral budding and virus maturation were described as direct ESCRT contexts but non-core for this proteostasis review.

Pn Notes

(MVB12B-pn-notes.md)

MVB12B PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q9H7P6
AIGR review status: COMPLETE
Review batch: proteostasis-pr-1217 (PR 1217)
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/MVB12B/MVB12B-ai-review.yaml
AIGR review HTML: present - genes/human/MVB12B/MVB12B-ai-review.html
Gene notes: present - genes/human/MVB12B/MVB12B-notes.md
GOA TSV: present - genes/human/MVB12B/MVB12B-goa.tsv
UniProt record: present - genes/human/MVB12B/MVB12B-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/MVB12B.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/MVB12B.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

Description: MVB12B is a metazoan ESCRT-I fourth subunit that complexes with TSG101, VPS28, and VPS37-family subunits. Its best-supported core cellular role is ESCRT-I-dependent sorting of ubiquitinated endosomal cargo into multivesicular bodies, supported by MABP acidic-phospholipid binding and ESCRT-I composition evidence. Viral budding and virus maturation reflect pathogen exploitation of ESCRT machinery rather than the main endogenous MVB12B function.
Existing/core annotation action counts: ACCEPT: 15; KEEP_AS_NON_CORE: 12; MARK_AS_OVER_ANNOTATED: 3; MODIFY: 2

PN Consistency Summary

Consistency: Two issues. (1) GO:0000813 ESCRT I complex is consistent (ACCEPTed). (2) The PN new_to_goa projection of GO:0000045 autophagosome assembly has no support in the MVB12B review or GOA, and parallels MVB12A where macroautophagy is MARK_AS_OVER_ANNOTATED — so PN over-reaches here. (3) Internal review bug: the GO:0043130 ubiquitin binding row is correctly flagged negated: true (GOA = NOT|enables ... IDA PMID:20654576, an experimental NOT call) yet given action: UNDECIDED with reason "cannot be confirmed... before accepting or removing." The curator experimentally established NON-binding; per project rules this NOT annotation should be ACCEPTed (retained), not left UNDECIDED.
PN story / NEW pressure: PN asserts a brand-new autophagosome-assembly role for MVB12B (new_to_goa) via ESCRT-I sealing. No MVB12B-specific evidence supports it; the shared structural paper assays VPS28, and phagophore-closure ESCRT evidence (PMID:31519728) is for VPS37A. Conclusion: over-reaches; defer to expert question rather than annotate.
Evidence alignment: Shared: PMID:32424346 (ESCRT-I scaffold) underpins both PN row and review CC/fission annotations; PMID:20654576 (MVB12A/B PTMs) is the basis of both the EGFR-context and the negated ubiquitin-binding row. Overlap strong; divergence only on autophagy inference.
Verdict: ESCRT-I membership consistent; PN GO:0000045 (new_to_goa) over-reaches; review has a negation/action inconsistency. Recommended edits: in MVB12B YAML, change the GO:0043130 ubiquitin binding row from action: UNDECIDED to ACCEPT (retain the experimental NOT annotation; GOA NOT|enables IDA PMID:20654576) and fix the summary to reflect NON-binding rather than "cannot be confirmed." Flag the "Sealing" node so GO:0000045 is not auto-propagated to MVB12B.

Full Consistency Review

UniProt: Q9H7P6 · batch: proteostasis-pr-1217 · review status: COMPLETE
PN placement: ALP|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component ; PN-node mapping: leaf mapped / GO:0000813 ESCRT I complex; "Sealing" group mapped / ok_for_propagation / GO:0000045 autophagosome assembly; class context_only GO:0016236. Projected: GO:0000813 (already_in_goa_exact), GO:0000045 (new_to_goa).
Consistency: Two issues. (1) GO:0000813 ESCRT I complex is consistent (ACCEPTed). (2) The PN new_to_goa projection of GO:0000045 autophagosome assembly has no support in the MVB12B review or GOA, and parallels MVB12A where macroautophagy is MARK_AS_OVER_ANNOTATED — so PN over-reaches here. (3) Internal review bug: the GO:0043130 ubiquitin binding row is correctly flagged negated: true (GOA = NOT|enables ... IDA PMID:20654576, an experimental NOT call) yet given action: UNDECIDED with reason "cannot be confirmed... before accepting or removing." The curator experimentally established NON-binding; per project rules this NOT annotation should be ACCEPTed (retained), not left UNDECIDED.
PN story / NEW pressure: PN asserts a brand-new autophagosome-assembly role for MVB12B (new_to_goa) via ESCRT-I sealing. No MVB12B-specific evidence supports it; the shared structural paper assays VPS28, and phagophore-closure ESCRT evidence (PMID:31519728) is for VPS37A. Conclusion: over-reaches; defer to expert question rather than annotate.
Mapping strategy: Same as MVB12A — the "Sealing" node's blanket ok_for_propagation of GO:0000045 to every ESCRT-I-component leaf is too strong for MVB12B (membership ≠ demonstrated closure function). Recommend candidate-only propagation.
Evidence alignment: Shared: PMID:32424346 (ESCRT-I scaffold) underpins both PN row and review CC/fission annotations; PMID:20654576 (MVB12A/B PTMs) is the basis of both the EGFR-context and the negated ubiquitin-binding row. Overlap strong; divergence only on autophagy inference.
Verdict: ESCRT-I membership consistent; PN GO:0000045 (new_to_goa) over-reaches; review has a negation/action inconsistency. Recommended edits: in MVB12B YAML, change the GO:0043130 ubiquitin binding row from action: UNDECIDED to ACCEPT (retain the experimental NOT annotation; GOA NOT|enables IDA PMID:20654576) and fix the summary to reflect NON-binding rather than "cannot be confirmed." Flag the "Sealing" node so GO:0000045 is not auto-propagated to MVB12B.

PN Dossier Context

review_batch: proteostasis-pr-1217
review_yaml: genes/human/MVB12B/MVB12B-ai-review.yaml
PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-I complex component

UniProt: Q9H7P6
In branches: ALP
Notes: Component of the ESCRT-I complex, involved in autophagosome closure
PN references (titles):
- A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission | Nature Structural & Molecular Biology
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000813 ESCRT I complex]
  rationale: This leaf is restricted to ESCRT-I components used in autophagophore sealing. The shared GO assertion is ESCRT I complex membership.
- [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
  rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
- [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (2)

GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
GO:0000813 ESCRT I complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q9H7P6
gene_symbol: MVB12B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  MVB12B is a metazoan ESCRT-I fourth subunit that complexes with TSG101, VPS28, and VPS37-family
  subunits. Its best-supported core cellular role is ESCRT-I-dependent sorting of ubiquitinated
  endosomal cargo into multivesicular bodies, supported by MABP acidic-phospholipid binding and
  ESCRT-I composition evidence. Viral budding and virus maturation reflect pathogen exploitation of
  ESCRT machinery rather than the main endogenous MVB12B function.
alternative_products:
- name: '1'
  id: Q9H7P6-1
- name: '2'
  id: Q9H7P6-2
  sequence_note: VSP_020364
existing_annotations:
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central MVB12B cellular-component annotation.
    action: ACCEPT
    reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence.
    additional_reference_ids: &id007
    - PMID:18005716
    - PMID:20654576
    - file:human/MVB12B/MVB12B-uniprot.txt
    - file:human/MVB12B/MVB12B-notes.md
    - file:human/MVB12B/MVB12B-deep-research-falcon.md
    supported_by: &id008
    - &id013
      reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: Component of the ESCRT-I complex
    - &id014
      reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: which consists of TSG101, VPS28, a VPS37
    - &id015
      reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: Interacts with TSG101
    - &id016
      reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: Interacts with VPS28
    - &id017
      reference_id: PMID:18005716
      supporting_text: constitute the fourth class of metazoan ESCRT-I subunits
    - &id018
      reference_id: PMID:18005716
      supporting_text: one copy of each of the four subunit types
    - &id019
      reference_id: PMID:18005716
      supporting_text: associate with the core region of the binary TSG101-VPS37 complex
    - &id020
      reference_id: PMID:20654576
      supporting_text: MVB12A and MVB12B are subunits of ESCRT-I
    - reference_id: file:human/MVB12B/MVB12B-deep-research-falcon.md
      supporting_text: structural component of the ESCRT-I
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: late endosome localization is supported and relevant to MVB12B/ESCRT-I function.
    action: ACCEPT
    reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting.
    additional_reference_ids: &id003
    - PMID:22232651
    - file:human/MVB12B/MVB12B-uniprot.txt
    - file:human/MVB12B/MVB12B-notes.md
    supported_by: &id004
    - &id025
      reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: Endosome
    - &id026
      reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: Late endosome membrane
    - &id027
      reference_id: PMID:22232651
      supporting_text: function both in protein transport at endosomes
- term:
    id: GO:0019075
    label: virus maturation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: virus maturation is directly supported but is a non-core host-pathogen context for this review.
    action: KEEP_AS_NON_CORE
    reason: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal
      ESCRT-I cargo sorting.
    additional_reference_ids: &id001
    - PMID:18005716
    - file:human/MVB12B/MVB12B-notes.md
    supported_by: &id002
    - reference_id: PMID:18005716
      supporting_text: MVB12 depletion and overexpression inhibit HIV-1 infectivity
    - reference_id: PMID:18005716
      supporting_text: aberrant virion morphologies and altered viral Gag protein processing
- term:
    id: GO:0042058
    label: regulation of epidermal growth factor receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: EGF/EGFR pathway context is supported but secondary for MVB12B.
    action: KEEP_AS_NON_CORE
    reason: PMID:20654576 links MVB12B post-translational regulation to EGF stimulation and ESCRT-I function, but EGFR regulation
      is a substrate/context-specific consequence rather than the core function.
    additional_reference_ids: &id011
    - PMID:20654576
    - file:human/MVB12B/MVB12B-notes.md
    supported_by: &id012
    - reference_id: PMID:20654576
      supporting_text: increased upon EGF stimulation
    - reference_id: PMID:20654576
      supporting_text: led to the instability and inclusion of MVB12B
- term:
    id: GO:0046755
    label: viral budding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: viral budding is directly supported but is a non-core host-pathogen context for this review.
    action: KEEP_AS_NON_CORE
    reason: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal
      ESCRT-I cargo sorting.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: cytoplasm is supported as a localization/context row but is not the core MVB12B function.
    action: KEEP_AS_NON_CORE
    reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad.
    additional_reference_ids: &id009
    - PMID:19056867
    - PMID:22232651
    - file:human/MVB12B/MVB12B-uniprot.txt
    - file:human/MVB12B/MVB12B-notes.md
    supported_by: &id010
    - reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: Cytoplasm
    - reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: Nucleus
    - reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: plasma membrane
    - reference_id: PMID:22232651
      supporting_text: autonomously localizing to subcellular puncta and to the plasma membrane
    - reference_id: PMID:19056867
      supporting_text: Large-scale proteomics and phosphoproteomics of urinary exosomes
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: endosome localization is supported and relevant to MVB12B/ESCRT-I function.
    action: ACCEPT
    reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: late endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function.
    action: ACCEPT
    reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent MVB12B function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context,
      not generic protein binding from broad interaction screens.
    proposed_replacement_terms:
    - id: GO:0000813
      label: ESCRT I complex
    additional_reference_ids: &id005
    - PMID:25416956
    - PMID:28514442
    - PMID:33961781
    - file:human/MVB12B/MVB12B-notes.md
    supported_by: &id006
    - reference_id: file:human/MVB12B/MVB12B-notes.md
      supporting_text: broad localization/context rows but are not the core proteostasis function
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent MVB12B function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context,
      not generic protein binding from broad interaction screens.
    proposed_replacement_terms:
    - id: GO:0000813
      label: ESCRT I complex
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent MVB12B function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context,
      not generic protein binding from broad interaction screens.
    proposed_replacement_terms:
    - id: GO:0000813
      label: ESCRT I complex
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0046755
    label: viral budding
  evidence_type: IMP
  original_reference_id: PMID:18005716
  qualifier: involved_in
  review:
    summary: viral budding is directly supported but is a non-core host-pathogen context for this review.
    action: KEEP_AS_NON_CORE
    reason: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal
      ESCRT-I cargo sorting.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-184269
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function.
    action: ACCEPT
    reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3149434
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function.
    action: ACCEPT
    reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3159232
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function.
    action: ACCEPT
    reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917696
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function.
    action: ACCEPT
    reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917730
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function.
    action: ACCEPT
    reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0019075
    label: virus maturation
  evidence_type: IMP
  original_reference_id: PMID:18005716
  qualifier: involved_in
  review:
    summary: virus maturation is directly supported but is a non-core host-pathogen context for this review.
    action: KEEP_AS_NON_CORE
    reason: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal
      ESCRT-I cargo sorting.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:18005716
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central MVB12B cellular-component annotation.
    action: ACCEPT
    reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence.
    additional_reference_ids: *id007
    supported_by: *id008
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:20654576
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central MVB12B cellular-component annotation.
    action: ACCEPT
    reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence.
    additional_reference_ids: *id007
    supported_by: *id008
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20654576
  qualifier: enables
  review:
    summary: Protein binding should be replaced by ESCRT-I complex membership.
    action: MODIFY
    reason: The cited MVB12A/B paper supports ESCRT-I subunit/complex membership rather than a standalone generic protein-binding
      function.
    proposed_replacement_terms:
    - id: GO:0000813
      label: ESCRT I complex
    additional_reference_ids: *id007
    supported_by: *id008
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:22232651
  qualifier: located_in
  review:
    summary: nucleus is supported as a localization/context row but is not the core MVB12B function.
    action: KEEP_AS_NON_CORE
    reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad.
    additional_reference_ids: *id009
    supported_by: *id010
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:22232651
  qualifier: located_in
  review:
    summary: early endosome localization is supported and relevant to MVB12B/ESCRT-I function.
    action: ACCEPT
    reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:22232651
  qualifier: located_in
  review:
    summary: late endosome localization is supported and relevant to MVB12B/ESCRT-I function.
    action: ACCEPT
    reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:22232651
  qualifier: located_in
  review:
    summary: cytosol is supported as a localization/context row but is not the core MVB12B function.
    action: KEEP_AS_NON_CORE
    reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad.
    additional_reference_ids: *id009
    supported_by: *id010
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:22232651
  qualifier: located_in
  review:
    summary: plasma membrane is supported as a localization/context row but is not the core MVB12B function.
    action: KEEP_AS_NON_CORE
    reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad.
    additional_reference_ids: *id009
    supported_by: *id010
- term:
    id: GO:0008289
    label: lipid binding
  evidence_type: IMP
  original_reference_id: PMID:22232651
  qualifier: enables
  review:
    summary: Lipid binding is correct but should be made more specific.
    action: MODIFY
    reason: MVB12A/MVB12B MABP domains bind acidic phospholipid-containing liposomes, so phospholipid binding is the more
      informative MF term.
    proposed_replacement_terms:
    - id: GO:0005543
      label: phospholipid binding
    additional_reference_ids:
    - PMID:22232651
    - file:human/MVB12B/MVB12B-notes.md
    supported_by:
    - &id028
      reference_id: PMID:22232651
      supporting_text: MABP domains of the MVB12A and B subunits
    - &id029
      reference_id: PMID:22232651
      supporting_text: bind in vitro to liposomes containing acidic lipids
    - &id030
      reference_id: PMID:22232651
      supporting_text: coincidence detector for acidic phospholipids and protein ligands
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: IDA
  original_reference_id: PMID:20654576
  qualifier: located_in
  review:
    summary: vesicle is supported as a localization/context row but is not the core MVB12B function.
    action: KEEP_AS_NON_CORE
    reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad.
    additional_reference_ids: *id009
    supported_by: *id010
- term:
    id: GO:0042058
    label: regulation of epidermal growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:20654576
  qualifier: involved_in
  review:
    summary: EGF/EGFR pathway context is supported but secondary for MVB12B.
    action: KEEP_AS_NON_CORE
    reason: PMID:20654576 links MVB12B post-translational regulation to EGF stimulation and ESCRT-I function, but EGFR regulation
      is a substrate/context-specific consequence rather than the core function.
    additional_reference_ids: *id011
    supported_by: *id012
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IDA
  original_reference_id: PMID:20654576
  qualifier: enables
  negated: true
  review:
    summary: MVB12B does NOT bind ubiquitin; this is an experimentally-supported negated (NOT) annotation.
    action: ACCEPT
    reason: This is a curator-made experimental NOT|enables IDA (negated=true) from PMID:20654576, i.e. the curator
      established that MVB12B does not directly bind ubiquitin (in ESCRT-I, the TSG101 UEV domain provides ubiquitin
      binding). The negation is the finding and should be accepted, deferring to the curator's full-text reading rather
      than left undecided; the cached abstract foregrounds MVB12B ubiquitination, which is a different assay.
    additional_reference_ids:
    - PMID:20654576
    - file:human/MVB12B/MVB12B-notes.md
    supported_by:
    - reference_id: PMID:20654576
      supporting_text: ubiquitination of Lys264 and Lys290 of MVB12B
    - reference_id: file:human/MVB12B/MVB12B-notes.md
      supporting_text: The negated ubiquitin-binding row is therefore ACCEPTed as the experimentally-supported non-binding finding
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IC
  original_reference_id: PMID:20654576
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part
      of MVB12B/ESCRT-I endosomal cargo sorting.
    action: ACCEPT
    reason: MVB12B/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/MVB12B/MVB12B-uniprot.txt
    - file:human/MVB12B/MVB12B-notes.md
    - file:human/MVB12B/MVB12B-deep-research-falcon.md
    supported_by:
    - &id021
      reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: Required for the sorting of endocytic
    - &id022
      reference_id: file:human/MVB12B/MVB12B-uniprot.txt
      supporting_text: ubiquitinated cargos into multivesicular bodies
    - &id023
      reference_id: PMID:18005716
      supporting_text: plays essential roles in HIV budding and endosomal protein sorting
    - &id024
      reference_id: PMID:20654576
      supporting_text: sorting of ubiquitinated cargo protein from the plasma membrane to the endosomal vesicle
    - reference_id: file:human/MVB12B/MVB12B-deep-research-falcon.md
      supporting_text: MVB12B fulfills an adaptor/scaffold role in recognizing and sorting ubiquitinated membrane proteins into intraluminal vesicles
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: extracellular exosome is supported as a localization/context row but is not the core MVB12B function.
    action: KEEP_AS_NON_CORE
    reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad.
    additional_reference_ids: *id009
    supported_by: *id010
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative
    changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:18005716
  title: Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding.
  findings: []
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:20654576
  title: Distinct functions of human MVB12A and MVB12B in the ESCRT-I dependent on their posttranslational modifications.
  findings: []
- id: PMID:22232651
  title: "Structural basis for membrane targeting by the MVB12-associated \u03B2-prism domain of the human ESCRT-I MVB12 subunit."
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: Reactome:R-HSA-184269
  title: Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by the ESCRT-I complex
  findings: []
- id: Reactome:R-HSA-3149434
  title: Transport of GAG to the Plasma Membrane
  findings: []
- id: Reactome:R-HSA-3159232
  title: Recruitment Of HIV Virion Budding Machinery
  findings: []
- id: Reactome:R-HSA-917696
  title: Cargo Sequestration
  findings: []
- id: Reactome:R-HSA-917730
  title: Cargo Recognition And Sorting
  findings: []
- id: file:human/MVB12B/MVB12B-uniprot.txt
  title: UniProtKB record for human MVB12B
  findings: []
- id: file:human/MVB12B/MVB12B-notes.md
  title: MVB12B review notes
  findings: []
- id: file:human/MVB12B/MVB12B-deep-research-falcon.md
  title: Falcon deep research report for MVB12B
  findings: []
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: >-
      LLM-synthesized deep-research report (Edison/Falcon); not independently
      verified against primary full text, so marked UNVERIFIED. MVB12B-SPECIFIC and
      well-anchored: (1) MVB12B is a fourth-subunit ESCRT-I member that acts as a
      structural/adaptor subunit in sorting ubiquitinated cargo into MVBs, and (2) the
      TBK1/STING-dependent phosphorylation of MVB12B (S222) that drives sorting of DNA
      into extracellular vesicles for paracrine cGAS-STING signaling (Nandakumar 2019;
      Kuchitsu 2023) -- this immune/EV-sorting axis is a genuine MVB12B-specific
      function not currently captured in the GOA rows. CAUTION: many statements about
      cytokinesis/abscission, autophagosome closure, membrane repair, and broad
      enveloped-virus egress are explicitly flagged in the report as ESCRT-I
      holo-complex level (or MVB12A-paralog structural inference, e.g. the human ESCRT-I
      head structure was solved with MVB12A not MVB12B) rather than MVB12B-specific, and
      should not be attributed to the MVB12B subunit. Used here only to corroborate the
      MVB12B adaptor/cargo-sorting and ESCRT-I-membership annotations, not to add
      holo-complex processes.
core_functions:
- description: MVB12B is a fourth subunit of metazoan ESCRT-I complexes and helps organize MVB12B-containing TSG101-VPS28-VPS37
    assemblies for endosomal cargo sorting.
  directly_involved_in:
  - id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  locations:
  - id: GO:0005768
    label: endosome
  - id: GO:0010008
    label: endosome membrane
  - id: GO:0031902
    label: late endosome membrane
  in_complex:
    id: GO:0000813
    label: ESCRT I complex
  supported_by:
  - *id013
  - *id014
  - *id015
  - *id016
  - *id017
  - *id018
  - *id019
  - *id020
  - *id021
  - *id022
  - *id023
  - *id024
  - *id025
  - *id026
  - *id027
- description: MVB12B MABP-domain acidic phospholipid binding supports ESCRT-I membrane targeting context.
  molecular_function:
    id: GO:0005543
    label: phospholipid binding
  directly_involved_in:
  - id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  locations:
  - id: GO:0005769
    label: early endosome
  - id: GO:0005770
    label: late endosome
  in_complex:
    id: GO:0000813
    label: ESCRT I complex
  supported_by:
  - *id028
  - *id029
  - *id030
  - *id013
  - *id014
  - *id015
  - *id016
  - *id017
  - *id018
  - *id019
  - *id020
proposed_new_terms: []
suggested_questions:
- question: Should MVB12B ubiquitin binding be accepted only after full-text confirmation of PMID:20654576, or should this
    row be removed as a conflation with MVB12B ubiquitination?
  experts:
  - GO molecular function editors
  - UniProt curators
- question: Should MVB12B generic protein-binding annotations be replaced by ESCRT-I complex membership and phospholipid binding
    where the evidence supports those more specific terms?
  experts:
  - GO molecular function editors
  - GO ESCRT curators
- question: Does the TBK1/STING-dependent phosphorylation of MVB12B (reportedly at S222) that drives sorting of cytosolic DNA into
    extracellular vesicles for paracrine cGAS-STING signaling (Nandakumar 2019, Kuchitsu 2023, summarized in the falcon deep-research
    report) warrant an MVB12B-specific innate-immune / extracellular-vesicle cargo-loading annotation, once the primary full text is
    verified? This MVB12B-specific axis is not currently captured in the GOA rows.
  experts:
  - GO biological process editors
  - GO immunology curators
suggested_experiments:
- experiment_type: MVB12B molecular-function refinement
  hypothesis: MVB12B membrane recognition is better represented by phospholipid binding than generic protein binding, while
    ubiquitin binding requires direct confirmation.
  description: Test purified MVB12B MABP/UMA regions for acidic phospholipid binding and ubiquitin binding using matched mutants,
    then measure rescue in endosomal cargo-sorting assays.
- experiment_type: MVB12 paralog ESCRT-I sorting comparison
  hypothesis: MVB12A and MVB12B differ in endosomal cargo-sorting and EGF-stimulated post-translational regulation.
  description: Compare MVB12A and MVB12B knockout/rescue in EGFR degradation, ESCRT-I recruitment, and HIV budding assays
    under matched expression conditions.

MVB12B

Gene Description

Existing Annotations Review

Core Functions

MVB12B is a fourth subunit of metazoan ESCRT-I complexes and helps organize MVB12B-containing TSG101-VPS28-VPS37 assemblies for endosomal cargo sorting.

MVB12B MABP-domain acidic phospholipid binding supports ESCRT-I membrane targeting context.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Functional Annotation of Human MVB12B (UniProt: Q9H7P6)

1. Key Concepts and Definitions

2. Recent Developments and Latest Research (2023–2024 priority)

3. Cellular Localization and Function

4. Biological Pathways and Real-world Relevance

Multivesicular Body Biogenesis & Exosome Formation

Viral Budding & Pathogen Interaction

Immune Pathways (STING–TBK1–MVB12B Axis)

Cell Division and Membrane Repair

Autophagy and Lysosomal Trafficking

5. Expert Opinions, Analyses, and Relevant Data

6. Structured Summaries

7. Citation List, URLs, and Publication Dates (Selection)

8. Conclusion

Artifacts

Citations

📚 Additional Documentation

Notes

MVB12B review notes

Scope

Evidence synthesis

Falcon

Description cleanup note

Pn Notes

MVB12B PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-I complex component

Projected GO annotations (2)

Note

📄 View Raw YAML