Affinage

RAB7B

Ras-related protein Rab-7b · UniProt Q96AH8

Length
199 aa
Mass
22.5 kDa
Annotated
2026-06-10
23 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB7B is a late endosome/lysosome-localized small GTPase that governs retrograde membrane traffic from late endosomes to the trans-Golgi network and, through this control of lysosomal trafficking, modulates innate immune signaling, autophagy, and cell migration (PMID:20375062, PMID:17395780). Cycling between a lysosome-associated wild-type pool and a Golgi-localized GTP-bound state, RAB7B controls retrieval of the cargo receptors CI-MPR and sortilin — with which it interacts directly — back to the TGN, and its loss disrupts cathepsin-D maturation and lysosomal enzyme delivery (PMID:20375062, PMID:22708738). Its GTPase cycle is terminated by the GAP TBC1D5, which binds RAB7B and exhibits GAP activity that is potentiated by retromer, such that TBC1D5 depletion phenocopies constitutively active RAB7B in CI-MPR/sortilin vesicle distribution (PMID:30111580). In macrophages, RAB7B drives lysosomal degradation of activated TLR4 and TLR9, thereby attenuating LPS- and CpG-induced MAPK, NF-κB, and IRF3 signaling and cytokine output (PMID:17395780, PMID:19587007). RAB7B additionally links lysosomes to the actomyosin cytoskeleton: it interacts directly with myosin II and with the lysosomal Ca²⁺ channel TRPML1, controlling RhoA activity and myosin light-chain phosphorylation to support stress-fiber formation, adhesion, and dendritic-cell migration (PMID:25217632, PMID:34494097). It also restrains autophagy by binding the protease Atg4B and limiting LC3 processing (PMID:28835545).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2004 Medium

    Established RAB7B as a distinct lysosome-localized small GTPase with a cell-type-restricted expression pattern, defining the organelle and lineage context for all later mechanistic work.

    Evidence Immunofluorescence, RT-PCR, and overexpression in monocytic cell lines

    PMID:15144907

    Open questions at the time
    • No biochemical demonstration of GTPase activity
    • Molecular effectors and traffic step undefined
  2. 2007 High

    Answered what RAB7B does in immune cells by showing it routes activated TLR4 to lysosomes for degradation, defining a negative-feedback role in innate immune signaling.

    Evidence Reciprocal overexpression/knockdown in macrophages with TLR4 protein, cytokine, and pathway readouts

    PMID:17395780

    Open questions at the time
    • Adaptor linking RAB7B to TLR4 cargo not identified
    • GTPase cycle requirement not tested here
  3. 2009 High

    Generalized the immune-regulatory mechanism by showing RAB7B also degrades TLR9 and is itself transcriptionally suppressed downstream of TLR9 activation, revealing a regulatory loop.

    Evidence Colocalization, knockdown/overexpression, cytokine ELISA and kinase assays in macrophages

    PMID:19587007

    Open questions at the time
    • Selectivity for which receptor cargoes is degraded unresolved
    • Mechanism of ERK/p38-mediated Rab7b suppression not detailed
  4. 2010 High

    Defined the core trafficking activity of RAB7B as retrograde transport from late endosomes to the TGN, coupling its GTP state to Golgi localization and to lysosomal enzyme delivery.

    Evidence siRNA, dominant-negative (T22N) and constitutively active (Q67L) mutants, cargo-specific assays including cholera toxin and VSV-G controls

    PMID:20375062

    Open questions at the time
    • Direct cargo receptors not yet identified
    • Tubulation/carrier machinery undefined
  5. 2012 High

    Identified the specific cargoes of RAB7B-dependent retrieval, showing it directly binds sortilin and controls both CI-MPR and sortilin retrieval and TGN carrier formation.

    Evidence Mutant expression, endosome-to-Golgi retrieval assays, live imaging, Rab7b-sortilin co-IP

    PMID:22708738

    Open questions at the time
    • Whether sortilin binding is direct vs complex-mediated not structurally resolved
    • GAP/GEF controlling the cycle still unknown
  6. 2010 Medium

    Extended RAB7B function to hematopoietic differentiation, linking it to NF-κB/IL-6 signaling and STAT3-GATA-1 association during megakaryocytic differentiation.

    Evidence siRNA/overexpression, pathway inhibitors, STAT3-GATA-1 co-IP, differentiation marker flow cytometry

    PMID:20953574

    Open questions at the time
    • Connection between trafficking role and NF-κB activation mechanistically unclear
    • Single lineage context
  7. 2014 High

    Connected RAB7B to the cytoskeleton by establishing direct binding to myosin II and control of RhoA/MLC signaling, explaining how RAB7B vesicles move and how it influences adhesion and migration.

    Evidence Pulldown for direct interaction, myosin II depletion/inhibition, RhoA and MLC phosphorylation assays, migration assays

    PMID:25217632

    Open questions at the time
    • Direct vs indirect basis of RhoA regulation unresolved
    • How GTPase cycle gates myosin engagement unknown
  8. 2017 High

    Revealed a role in autophagy regulation: RAB7B binds the protease Atg4B and restrains LC3 processing, so its loss elevates autophagic flux.

    Evidence Rab7b-Atg4B co-IP, colocalization, siRNA knockdown with multiple autophagic flux readouts

    PMID:28835545

    Open questions at the time
    • Whether binding directly inhibits Atg4B catalysis not shown biochemically
    • Link to retrograde trafficking role unclear
  9. 2018 High

    Identified TBC1D5 as the GAP that terminates the RAB7B GTPase cycle, with retromer potentiation, placing RAB7B in a defined regulatory circuit for CI-MPR/sortilin retrieval.

    Evidence TBC-domain siRNA screen, in vitro GAP assay, TBC1D5-Rab7b co-IP, vesicle-number phenotypes

    PMID:30111580

    Open questions at the time
    • GEF activating RAB7B not identified
    • Structural basis of TBC1D5-retromer-Rab7b coupling unresolved
  10. 2020 Medium

    Demonstrated a tissue-specific function in keratinocytes, where RAB7B is required for degradation of incorporated melanosomes.

    Evidence Rab localization screen, CRISPR/Cas9 KO and siRNA with melanosome protein degradation probe

    PMID:32037382

    Open questions at the time
    • Molecular effectors on melanosomes unidentified
    • Relation to TGN retrieval role unclear
  11. 2021 High

    Integrated lysosomal and cytoskeletal roles by showing RAB7B binds TRPML1 to enable local myosin II activation and TFEB signaling driving dendritic-cell migration.

    Evidence Rab7b KO/KD in dendritic cells, 3D migration assays, Rab7b-TRPML1 co-IP, MLC phosphorylation and TFEB assays

    PMID:34494097

    Open questions at the time
    • How Ca2+ flux through TRPML1 is spatially restricted by RAB7B not resolved
    • Direct vs indirect TFEB regulation unclear
  12. 2023 Medium

    Implicated RAB7B in oligodendroglial differentiation, where its knockdown rescues ER-stress-impaired morphological differentiation, distinguishing it from RAB7A.

    Evidence siRNA of Rab7B vs Rab7A in a tunicamycin ER-stress model with differentiation markers

    PMID:37248316

    Open questions at the time
    • Mechanism linking RAB7B to ER stress/differentiation undefined
    • Single cell-line model
  13. 2024 Medium

    Extended the oligodendroglial role to disease, showing RAB7B knockdown rescues morphology in cells expressing a PMD-associated PLP1 mutant and reroutes mutant PLP1 to lysosomes.

    Evidence CRISPR/CasRx knockdown with LAMP1 colocalization and morphology assays

    PMID:39280331

    Open questions at the time
    • Causal trafficking mechanism for mutant PLP1 not defined
    • Single model system

Open questions

Synthesis pass · forward-looking unresolved questions
  • The activating GEF for RAB7B and a unified structural model coupling its GTPase cycle to retrograde retrieval, cytoskeletal engagement, and Atg4B regulation remain undefined.
  • No GEF identified
  • No structure of RAB7B with its effectors
  • Mechanistic unification of trafficking, immune, and migration roles lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005764 lysosome 4 GO:0005794 Golgi apparatus 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-168256 Immune System 2 R-HSA-9609507 Protein localization 2 R-HSA-9612973 Autophagy 1
Partners
ATG4BMCOLN1MYH9SORT1TBC1D5TLR4TLR9

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 RAB7B (Rab7b) is a novel small GTPase that localizes to lysosomal organelles, as demonstrated by immunofluorescence confocal microscopy. It is selectively expressed in monocytes and monocyte-derived cells and is involved in PMA-induced monocytic differentiation of APL cells. Immunofluorescence confocal microscopy, Western blot, RT-PCR, overexpression in HL-60/NB4 cell lines Biochemical and biophysical research communications Medium 15144907
2007 Rab7b localizes to LAMP-1-positive (lysosomal) compartments and colocalizes with TLR4 after LPS treatment. Overexpression of Rab7b promotes lysosomal degradation of TLR4, thereby negatively regulating LPS-induced TNF-α, IL-6, nitric oxide, and IFN-β production, as well as MAP kinase, NF-κB, and IRF3 signaling in macrophages. Immunofluorescence colocalization, Western blot (TLR4 protein level), overexpression and knockdown in macrophages, cytokine measurement Blood High 17395780
2009 Late endosome/lysosome-localized Rab7b colocalizes with TLR9 in LAMP-1-positive compartments and promotes TLR9 degradation upon TLR9 activation, thereby negatively regulating TLR9-triggered TNF-α, IL-6, and IFN-β production and impairing MAPK and NF-κB pathway activation in macrophages. TLR9 ligation inhibits Rab7b expression via ERK and p38 activation. Immunofluorescence colocalization, Western blot (TLR9 protein levels), overexpression/knockdown in macrophages, cytokine ELISA, kinase activation assays Journal of immunology High 19587007
2010 Rab7b controls retrograde transport from late endosomes to the trans-Golgi network (TGN). Wild-type Rab7b is lysosome-associated, while GTP-bound (constitutively active) Rab7b localizes to the Golgi. Depletion or dominant-negative Rab7b T22N impairs cathepsin-D maturation, increases hexosaminidase secretion, alters TGN46 distribution, impairs CI-MPR trafficking, increases CI-MPR and cathepsin-D levels, and prevents cholera toxin B-subunit from reaching the Golgi. VSV-G trafficking is unaffected. Rab7b is not involved in EGF/EGFR degradation. siRNA knockdown, dominant-negative mutant expression (T22N), constitutively active mutant (Q67L), immunofluorescence, Western blot, hexosaminidase secretion assay, cholera toxin trafficking assay Journal of cell science High 20375062
2010 Rab7b promotes PMA-induced megakaryocytic differentiation by activating NF-κB-dependent IL-6 production and enhancing the association of activated STAT3 with GATA-1. Rab7b silencing impairs NF-κB activation, IL-6 production, and megakaryocytic differentiation markers. siRNA knockdown, overexpression, NF-κB inhibitor, IL-6 neutralizing antibody, STAT3-GATA-1 co-immunoprecipitation, flow cytometry for differentiation markers Journal of molecular medicine Medium 20953574
2012 Rab7b regulates retrograde transport of both CI-MPR and sortilin (a mannose-6-phosphate-independent sorting receptor) from late endosomes to the TGN. Rab7b interacts with sortilin directly. Expression of Rab7b mutants or silencing reduces CI-MPR and sortilin tubulation from TGN, and the constitutively active mutant Q67L impairs carrier formation from TGN. siRNA knockdown, constitutively active (Q67L) and dominant-negative (T22N) mutant expression, endosome-to-Golgi retrieval assays, immunofluorescence, live-cell imaging, co-immunoprecipitation (Rab7b-sortilin interaction) Traffic High 22708738
2014 Rab7b directly interacts with myosin II (actomyosin). Myosin II mediates transport of Rab7b-positive endosomes, as Rab7b vesicle dynamics are strongly impaired after myosin II depletion or inhibition. Rab7b also controls RhoA activation status, thereby regulating myosin light chain phosphorylation, stress fiber formation, cell adhesion, polarization, and migration. Co-immunoprecipitation/pulldown (direct interaction with myosin II), myosin II siRNA depletion, myosin II inhibition, live-cell imaging of Rab7b dynamics, RhoA activation assay, myosin light chain phosphorylation assay, cell migration assay Journal of cell science High 25217632
2017 Rab7b interacts with and co-localizes with the cysteine protease Atg4B on vesicles. Depletion of Rab7b increases autophagic flux (increased size of autophagic structures, increased macroautophagic sequestration and degradation). Rab7b negatively regulates autophagy by modulating Atg4B activity and thus LC3 processing. Co-immunoprecipitation (Rab7b-Atg4B interaction), colocalization by immunofluorescence, siRNA knockdown of Rab7b, autophagic flux assays (LC3 processing, sequestration/degradation assays) EMBO reports High 28835545
2018 TBC1D5 is a GTPase-activating protein (GAP) for Rab7b. TBC1D5 localizes to Rab7b-positive vesicles, physically interacts with Rab7b, and has GAP activity towards Rab7b in vitro; this GAP activity is further increased by retromer proteins. Silencing TBC1D5 reduces the number of CI-MPR- and sortilin-positive vesicles, phenocopying constitutively active Rab7b. An siRNA screen of TBC domain-containing proteins identified TBC1D5 as the strongest hit affecting Rab7b distribution. siRNA screen (TBC domain proteins), in vitro GAP activity assay, co-immunoprecipitation (TBC1D5-Rab7b), immunofluorescence colocalization, cell-based phenotypic assays (CI-MPR/sortilin vesicle number) Journal of cell science High 30111580
2020 Rab7B (also identified as Rab42) localizes to melanosome-containing compartments in keratinocytes and is required for protein degradation on incorporated melanosomes. Knockdown or CRISPR/Cas9 knockout of Rab7B strongly inhibits protein degradation on melanosomes in keratinocytes. Comprehensive Rab localization screen (Rab1–45), CRISPR/Cas9 knockout, siRNA knockdown, melanosome protein degradation assay (M-INK probe), immunofluorescence Cell structure and function Medium 32037382
2021 Rab7b links lysosomes to the actomyosin cytoskeleton to enable dendritic cell migration. Lack of Rab7b reduces myosin II light chain phosphorylation and activation of the transcription factor TFEB (required for lysosomal signaling and fast DC migration). Rab7b directly interacts with the lysosomal Ca2+ channel TRPML1 (MCOLN1), enabling local activation of myosin II at the cell rear. Rab7b knockout/knockdown in dendritic cells, 1D and 3D migration assays, co-immunoprecipitation (Rab7b-TRPML1 interaction), myosin light chain phosphorylation assay, TFEB activation assay Journal of cell science High 34494097
2023 Rab7B negatively regulates oligodendroglial cell morphological differentiation. Knockdown of Rab7B (but not Rab7A) recovers tunicamycin-induced ER stress-impaired morphological differentiation in FBD-102b oligodendroglial precursor cells, as measured by changes in differentiation- and myelination-related structural protein markers. siRNA knockdown of Rab7B and Rab7A, tunicamycin-induced ER stress model, morphological differentiation assay, Western blot for differentiation/myelination markers Journal of molecular neuroscience Medium 37248316
2024 Knockdown of Rab7B via CRISPR/CasRx restores incomplete cell shapes induced by the PMD-associated PLP1 p.Ala243Val mutation in oligodendroglial FBD-102b cells, and promotes trafficking of mutant PLP1 to LAMP1-positive organelles. CRISPR/CasRx-mediated Rab7B knockdown, immunofluorescence (LAMP1 colocalization), cell morphology assay Neuroscience insights Medium 39280331
2014 In thrombin-stimulated platelets, a calpain-myosin 9-Rab7b axis regulates TLR4-containing α-granule trafficking. Calpain cleaves myosin-9, and the interaction between TLR4 and myosin-9 is regulated by calpain. Co-IP indicated that myosin-9 does not coordinate with Rab7b to negatively regulate TLR4 trafficking in thrombin-treated platelets (negative finding for this specific context). Co-immunoprecipitation, flow cytometry (surface TLR4), Western blot, pharmacological inhibitors (calpeptin, TMB-8, U73122), transmission electron microscopy PloS one Low 24489676

Source papers

Stage 0 corpus · 23 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Lysosome-associated small Rab GTPase Rab7b negatively regulates TLR4 signaling in macrophages by promoting lysosomal degradation of TLR4. Blood 178 17395780
2010 Rab7b controls trafficking from endosomes to the TGN. Journal of cell science 108 20375062
2009 Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages. Journal of immunology (Baltimore, Md. : 1950) 56 19587007
2004 Rab7b, a novel lysosome-associated small GTPase, is involved in monocytic differentiation of human acute promyelocytic leukemia cells. Biochemical and biophysical research communications 55 15144907
2018 TBC1D5 controls the GTPase cycle of Rab7b. Journal of cell science 38 30111580
2014 A novel interaction between Rab7b and actomyosin reveals a dual role in intracellular transport and cell migration. Journal of cell science 38 25217632
2012 Dynamics of Rab7b-dependent transport of sorting receptors. Traffic (Copenhagen, Denmark) 36 22708738
2015 Trichuris suis soluble products induce Rab7b expression and limit TLR4 responses in human dendritic cells. Genes and immunity 32 25996526
2017 Rab7b modulates autophagic flux by interacting with Atg4B. EMBO reports 31 28835545
2010 Rab7b and receptors trafficking. Communicative & integrative biology 30 21057625
2014 The role of calpain-myosin 9-Rab7b pathway in mediating the expression of Toll-like receptor 4 in platelets: a novel mechanism involved in α-granules trafficking. PloS one 26 24489676
2020 Rab7B/42 Is Functionally Involved in Protein Degradation on Melanosomes in Keratinocytes. Cell structure and function 23 32037382
2021 Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton. Journal of cell science 22 34494097
2019 Rab7b Overexpression-Ameliorated Ischemic Brain Damage Following tMCAO Involves Suppression of TLR4 and NF-κB p65. Journal of molecular neuroscience : MN 22 30911939
2010 Small Rab GTPase Rab7b promotes megakaryocytic differentiation by enhancing IL-6 production and STAT3-GATA-1 association. Journal of molecular medicine (Berlin, Germany) 19 20953574
2022 Hyperthermia promotes exosome secretion by regulating Rab7b while increasing drug sensitivity in adriamycin-resistant breast cancer. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 14 35100921
2015 Rab7b at the intersection of intracellular trafficking and cell migration. Communicative & integrative biology 12 27066171
2024 Acetyl-11-keto-beta-boswellic acid inhibits cell proliferation and growth of oral squamous cell carcinoma via RAB7B-mediated autophagy. Toxicology and applied pharmacology 7 38513840
2019 Rab7b participation on the TLR4 (Toll-like receptor) endocytic pathway in Shiga toxin-associated Hemolytic Uremic Syndrome (HUS). Cytokine 7 31153054
2024 CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val. Neuroscience insights 4 39280331
2023 Knockdown of Rab7B, But Not of Rab7A, Which Antagonistically Regulates Oligodendroglial Cell Morphological Differentiation, Recovers Tunicamycin-Induced Defective Differentiation in FBD-102b Cells. Journal of molecular neuroscience : MN 3 37248316
2025 Therapeutic potential of T-cell receptor targeting the HLA-A*11:01-restricted KRASG12V neoantigen without cross-recognition of the self-antigen RAB7B in solid tumors. Journal for immunotherapy of cancer 2 40681176
2016 Site-directed mutagenesis, in vivo electroporation and mass spectrometry in search for determinants of the subcellular targeting of Rab7b paralogue in the model eukaryote Paramecium octaurelia. European journal of histochemistry : EJH 2 27349314

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