RAB7B

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005764 lysosome	IBA GO_REF:0000033	ACCEPT	Summary: RAB7B localizes to lysosomes and late endosomes, where it regulates trafficking to the trans-Golgi network. Wild-type Rab7b is lysosome-associated. Reason: This is a core localization for RAB7B. Multiple studies demonstrate RAB7B at late endosomes/lysosomes from which it controls retrograde transport to the TGN. Supporting Evidence: PMID:20375062 wild-type Rab7b is lysosome associated whereas an activated, GTP-bound form of Rab7b localizes to the Golgi apparatus
GO:0045335 phagocytic vesicle	IBA GO_REF:0000033	ACCEPT	Summary: RAB7B has been detected on phagocytic vesicles, consistent with its role in late endosomal/lysosomal trafficking and phagosome maturation. Reason: Phylogenetically conserved localization consistent with RAB7B's role in late endosomal trafficking that includes phagosomal compartments.
GO:0005770 late endosome	IBA GO_REF:0000033	ACCEPT	Summary: RAB7B localizes to late endosomes where it controls transport to the TGN. Reason: Late endosome localization is a core localization for RAB7B, well-documented in the primary literature. Supporting Evidence: PMID:20375062 Rab7b is required for normal lysosome function, and, in particular, that it is an essential factor for retrograde transport from endosomes to the trans-Golgi network (TGN)
GO:0008333 endosome to lysosome transport	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: RAB7B is involved in late endosomal trafficking, though its primary role is retrograde transport to the TGN rather than forward transport to lysosomes. Reason: While RAB7B is at late endosomes, its primary documented role is endosome-to-TGN retrograde transport rather than endosome-to-lysosome transport. This annotation may reflect phylogenetic inference from RAB7A functions.
GO:0090385 phagosome-lysosome fusion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phagosome-lysosome fusion is more characteristic of RAB7A than RAB7B. RAB7B's role in phagosome maturation appears to be related to trafficking rather than fusion per se. Reason: This may be phylogenetically inferred from RAB7A. RAB7B has been detected on phagosomes but its primary function is retrograde transport to TGN rather than phagosome-lysosome fusion.
GO:0000166 nucleotide binding	IEA GO_REF:0000043	ACCEPT	Summary: RAB7B binds GTP and GDP as part of its GTPase cycle that regulates membrane trafficking. Reason: Nucleotide binding is essential for RAB7B function as a small GTPase that cycles between GDP-bound and GTP-bound states.
GO:0002682 regulation of immune system process	IEA GO_REF:0000117	ACCEPT	Summary: RAB7B negatively regulates TLR4 and TLR9 signaling by promoting receptor trafficking toward degradation, and also promotes megakaryocyte differentiation through IL-6 signaling. Reason: RAB7B has documented roles in immune regulation through TLR signaling modulation and hematopoietic differentiation.
GO:0003924 GTPase activity	IEA GO_REF:0000002	ACCEPT	Summary: RAB7B is a small GTPase that hydrolyzes GTP to GDP to cycle between active and inactive states. TBC1D5 functions as a GTPase-activating protein (GAP) for RAB7B. Reason: GTPase activity is the core molecular function of RAB7B. The protein cycles between GTP-bound (active) and GDP-bound (inactive) states.
GO:0005525 GTP binding	IEA GO_REF:0000120	ACCEPT	Summary: RAB7B binds GTP in its active state, which determines its membrane localization and effector interactions. Reason: GTP binding is essential for RAB7B function as a molecular switch in membrane trafficking.
GO:0005764 lysosome	IEA GO_REF:0000120	ACCEPT	Summary: Duplicate annotation - lysosome localization consistent with IBA evidence. Reason: Consistent with IBA annotation and primary literature evidence.
GO:0005770 late endosome	IEA GO_REF:0000120	ACCEPT	Summary: Duplicate annotation - late endosome localization consistent with IBA evidence. Reason: Consistent with IBA annotation and primary literature evidence.
GO:0005794 Golgi apparatus	IEA GO_REF:0000044	ACCEPT	Summary: RAB7B localizes to the Golgi apparatus, particularly in its GTP-bound active state. Reason: Golgi localization is well-documented for RAB7B, especially the GTP-bound form. Supporting Evidence: PMID:20375062 wild-type Rab7b is lysosome associated whereas an activated, GTP-bound form of Rab7b localizes to the Golgi apparatus
GO:0015031 protein transport	IEA GO_REF:0000043	ACCEPT	Summary: RAB7B regulates protein transport, specifically retrograde transport from endosomes to the TGN. Reason: Protein transport regulation is the core biological process function of RAB7B.
GO:0030670 phagocytic vesicle membrane	IEA GO_REF:0000044	ACCEPT	Summary: RAB7B localizes to phagocytic vesicle membranes as part of phagosome maturation. Reason: Consistent with RAB7B's role in late endosomal/phagosomal trafficking.
GO:0031090 organelle membrane	IEA GO_REF:0000117	ACCEPT	Summary: RAB7B associates with organelle membranes including late endosomes, lysosomes, and Golgi. Reason: Broad localization term consistent with RAB7B's membrane-associated function.
GO:0031410 cytoplasmic vesicle	IEA GO_REF:0000043	ACCEPT	Summary: RAB7B localizes to cytoplasmic vesicles including late endosomes and transport vesicles. Reason: Consistent with RAB7B's role in vesicular trafficking.
GO:0045335 phagocytic vesicle	IEA GO_REF:0000120	ACCEPT	Summary: Duplicate annotation - phagocytic vesicle localization consistent with IBA evidence. Reason: Consistent with IBA annotation.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: This annotation is from a large-scale interactome mapping study (HuRI). Reason: Generic protein binding is uninformative. RAB7B's specific interactions with myosin II and TBC1D5 are more informative and should be annotated with specific terms. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome.
GO:0034144 negative regulation of toll-like receptor 4 signaling pathway	IEA GO_REF:0000107	ACCEPT	Summary: RAB7B negatively regulates TLR4 signaling by promoting receptor trafficking toward degradation in late endosomal/lysosomal compartments. Reason: Documented role of RAB7B in TLR4 negative regulation through its trafficking function.
GO:0034164 negative regulation of toll-like receptor 9 signaling pathway	IEA GO_REF:0000107	ACCEPT	Summary: RAB7B negatively regulates TLR9 signaling similar to TLR4. Reason: Documented role of RAB7B in TLR9 negative regulation.
GO:0003925 G protein activity	IMP PMID:20375062 Rab7b controls trafficking from endosomes to the TGN.	ACCEPT	Summary: PMID:20375062 demonstrated that RAB7B functions as a GTPase regulating endosome-to-TGN trafficking. Mutant analysis showed GTP-bound forms localize differently than wild-type. Reason: G protein activity is the core molecular function of RAB7B, demonstrated through dominant-negative mutant studies showing altered trafficking. Supporting Evidence: PMID:20375062 Expression of Rab7b T22N, a Rab7b dominant-negative mutant, impairs cathepsin-D maturation and causes increased secretion of hexosaminidase
GO:0031902 late endosome membrane	TAS Reactome:R-HSA-8854329	ACCEPT	Summary: Reactome pathway data places RAB7B at the late endosome membrane where TBC1D15 accelerates GTP hydrolysis. Reason: Consistent with RAB7B's established localization and GAP regulation.
GO:0045335 phagocytic vesicle	IDA PMID:21255211 Rab GTPases regulating phagosome maturation are differential...	ACCEPT	Summary: PMID:21255211 studied Rab GTPase recruitment to mycobacterial phagosomes and examined 42 distinct Rab GTPases including RAB7B. Reason: Consistent with other evidence for RAB7B at phagocytic vesicles. The study examined RAB7B along with other Rab proteins in phagosome maturation. Supporting Evidence: PMID:21255211 We compared the localization of 42 distinct Rab GTPases to phagosomes containing either Staphylococcus aureus or M. tb
GO:0005764 lysosome	IDA PMID:20375062 Rab7b controls trafficking from endosomes to the TGN.	ACCEPT	Summary: PMID:20375062 directly demonstrated that wild-type Rab7b is lysosome-associated through immunofluorescence and biochemical studies. Reason: Direct experimental evidence for lysosome localization. Supporting Evidence: PMID:20375062 wild-type Rab7b is lysosome associated whereas an activated, GTP-bound form of Rab7b localizes to the Golgi apparatus
GO:0005770 late endosome	IDA PMID:20375062 Rab7b controls trafficking from endosomes to the TGN.	ACCEPT	Summary: PMID:20375062 demonstrated RAB7B at late endosomes, where it controls retrograde transport. Reason: Direct experimental evidence for late endosome localization. Supporting Evidence: PMID:20375062 Rab7b is required for normal lysosome function, and, in particular, that it is an essential factor for retrograde transport from endosomes to the trans-Golgi network (TGN)
GO:0005794 Golgi apparatus	IDA PMID:20375062 Rab7b controls trafficking from endosomes to the TGN.	ACCEPT	Summary: PMID:20375062 showed that GTP-bound RAB7B localizes to the Golgi apparatus. Reason: Direct experimental evidence for Golgi localization of active RAB7B. Supporting Evidence: PMID:20375062 wild-type Rab7b is lysosome associated whereas an activated, GTP-bound form of Rab7b localizes to the Golgi apparatus
GO:0005802 trans-Golgi network	IDA PMID:20375062 Rab7b controls trafficking from endosomes to the TGN.	ACCEPT	Summary: PMID:20375062 demonstrated that RAB7B is essential for retrograde transport to the trans-Golgi network. Reason: TGN localization is a core component of RAB7B function. Supporting Evidence: PMID:20375062 Rab7b is required for normal lysosome function, and, in particular, that it is an essential factor for retrograde transport from endosomes to the trans-Golgi network (TGN)
GO:0032755 positive regulation of interleukin-6 production	IMP PMID:20953574 Small Rab GTPase Rab7b promotes megakaryocytic differentiati...	ACCEPT	Summary: PMID:20953574 demonstrated that Rab7b promotes IL-6 production through NF-kB activation during megakaryocytic differentiation. Reason: Direct experimental evidence that RAB7B promotes IL-6 production. Supporting Evidence: PMID:20953574 Rab7b promotes megakaryocytic differentiation by enhancing IL-6 production and STAT3-GATA-1 association
GO:0034144 negative regulation of toll-like receptor 4 signaling pathway	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation - TLR4 negative regulation consistent with IEA evidence. Reason: Consistent with established RAB7B function in TLR4 regulation.
GO:0034164 negative regulation of toll-like receptor 9 signaling pathway	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation - TLR9 negative regulation consistent with IEA evidence. Reason: Consistent with established RAB7B function in TLR9 regulation.
GO:0034499 late endosome to Golgi transport	IMP PMID:20375062 Rab7b controls trafficking from endosomes to the TGN.	ACCEPT	Summary: PMID:20375062 directly demonstrated that RAB7B is essential for retrograde transport from late endosomes to the TGN. Reason: This is the core biological process function of RAB7B, directly demonstrated through mutant and depletion studies. Supporting Evidence: PMID:20375062 Rab7b is required for normal lysosome function, and, in particular, that it is an essential factor for retrograde transport from endosomes to the trans-Golgi network (TGN)
GO:0045654 positive regulation of megakaryocyte differentiation	IMP PMID:20953574 Small Rab GTPase Rab7b promotes megakaryocytic differentiati...	KEEP AS NON CORE	Summary: PMID:20953574 demonstrated that Rab7b promotes PMA-induced megakaryocytic differentiation through IL-6/STAT3/GATA-1 signaling. Reason: This is a documented function but represents a cell-type specific role rather than the core trafficking function of RAB7B. Supporting Evidence: PMID:20953574 Rab7b, a late endosome/lysosome-localized myeloid small GTPase, promotes phorbol-12-myristate-13-acetate (PMA)-induced megakaryocytic differentiation
GO:0045159 myosin II binding	IPI PMID:25217632 A novel interaction between Rab7b and actomyosin reveals a d...	NEW	Summary: RAB7B directly binds myosin II, demonstrated through yeast two-hybrid screen, co-immunoprecipitation of endogenous proteins in human monocyte-derived dendritic cells, and recombinant protein pull-downs (Borg et al., 2014). Reason: This is a specific and informative molecular function annotation that should be added. The interaction is direct and functionally relevant to RAB7B's role in coupling endosomal transport to the actomyosin cytoskeleton. Supporting Evidence: file:human/RAB7B/RAB7B-deep-research-falcon.md Rab7b binds myosin II (validated by Y2H, co-IP of endogenous proteins in human MDDCs, and recombinant pull-downs) PMID:25217632 Sep 12. A novel interaction between Rab7b and actomyosin reveals a dual role in intracellular transport and cell migration.
GO:0030335 positive regulation of cell migration	IMP PMID:25217632 A novel interaction between Rab7b and actomyosin reveals a d...	NEW	Summary: RAB7B depletion reduces stress-fiber formation, cell adhesion on fibronectin, and delays migration. Mechanistically, RAB7B depletion lowers GTP-RhoA and decreases phosphorylated myosin light chain (Borg et al., 2014). Additionally, RAB7B links lysosomes to actin and is required for fast dendritic cell migration (Vestre et al., 2021). Reason: This is a well-documented function of RAB7B that links its trafficking role to cell migration through actomyosin regulation. Multiple studies support this annotation. Supporting Evidence: file:human/RAB7B/RAB7B-deep-research-falcon.md Rab7b depletion reduces stress-fiber formation, cell adhesion on fibronectin, and delays migration; mechanistically, Rab7b depletion lowers GTP-RhoA and decreases phosphorylated myosin light chain (MLC) PMID:25217632 Sep 12. A novel interaction between Rab7b and actomyosin reveals a dual role in intracellular transport and cell migration.

Gene Description

Existing Annotations Review

Core Functions

RAB7B functions as a small GTPase that regulates retrograde transport from late endosomes to the trans-Golgi network. It cycles between GTP-bound (active) and GDP-bound (inactive) states to control membrane trafficking.

RAB7B directly binds myosin II to couple endosomal transport to the actomyosin cytoskeleton, influencing cell adhesion, polarization, and migration through modulation of RhoA activation and myosin light chain phosphorylation.

References

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