RAB1B is the Rab GTPase of the early secretory pathway. Like all Rabs it is a nucleotide switch: prenylated at its C terminus, held in the cytosol by GDI when inactive, delivered to membranes and loaded with GTP by an exchange factor, and returned to the GDP state by a GTPase-activating protein. In the GTP state it recruits tethering factors that capture COPII-derived carriers leaving endoplasmic reticulum exit sites and hold them at the ER-Golgi intermediate compartment and cis-Golgi for fusion. Sustaining that flux is what keeps the Golgi ribbon compact, and knocking RAB1B down fragments the Golgi. RAB1B is largely redundant with its paralog RAB1A, and the genetics reflect this: phenotypes such as the block in herpes simplex virus 1 glycoprotein trafficking appear when both are removed and not when RAB1B alone is. Because autophagosome formation draws membrane and machinery from the early secretory pathway, RAB1B activity and functional ER exit sites are also required for autophagosomes to form, a requirement that sits upstream of the phagophore rather than on it. RAB1B is a favoured target of intracellular pathogens: Legionella pneumophila effectors recruit it to the bacterial vacuole, act as its exchange factor and covalently modify it.
Definition: The establishment of a barrier between epithelial cell layers of the intestine, mediated by tight junctions, that exerts specific and selective control over paracellular passage of water and solutes.
Justification: GOA carries a NOT|involved_in annotation of this gene to GO:0090557, which is defined for a barrier between endothelial cell layers of the intestine, citing PMID:23885123 - a study of intestinal epithelial tight junctions. GO has establishment of endothelial barrier, establishment of skin barrier, establishment of blood-brain barrier and establishment of Sertoli cell barrier, but nothing for the intestinal epithelial barrier, which is the most studied epithelial barrier there is. The absence forces epithelial results onto an endothelial term. The proposed_parent given here is the nearest existing sibling for orientation; the correct placement is alongside GO:0090557 under a shared barrier parent rather than beneath it.
Parent term: establishment of endothelial intestinal barrier
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003924 GTPase activity | IBA GO_REF:0000033 | ACCEPT | Summary: GTPase activity, the defining enzymatic activity of a Rab. Reason: RAB1B hydrolyses GTP, and this is what makes it a molecular switch rather than a constitutive binder. Supported by two independent EXP experiments including a structural study of the Rab-RabGAP transition state, plus IBA across the whole Rab family. Core. Supporting Evidence: PMID:23236136 Catalytic mechanism of a mammalian Rab |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Endoplasmic reticulum, the parent of the ER membrane term already annotated. Reason: A prenylated peripheral membrane GTPase is on the membrane, not in the lumen, so GO:0005789 is the informative term. Non-core. |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Golgi apparatus, the parent of the Golgi membrane term already annotated. Reason: Less informative than GO:0000139, which this gene carries. Non-core. |
| GO:0012505 endomembrane system | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Endomembrane system, propagated from about seventy donor genes across plants, fungi, flies, worms, Dictyostelium and mammals. Reason: The term covers essentially every intracellular membrane compartment, and the donor list spans most of the Rab family in most eukaryotic lineages. What it establishes is that Rabs act on membranes, which is definitional. Zero discriminating power for this gene, which already has four specific compartment membranes annotated. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001292747 · Rab GTPase superfamily node SUPPORTS TRANSFER Around seventy donor genes across plants, fungi, flies, worms, Dictyostelium and mammals, spanning most of the Rab family. The transfer is valid and the term is true; it simply says that Rabs act on intracellular membranes, which is definitional. Nothing about this gene follows from it that is not already stated by its four specific compartment-membrane annotations. |
| GO:0043025 neuronal cell body | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Neuronal cell body with an is_active_in qualifier, from a PANTHER node distinct from the one used for this gene's other IBAs. Reason: is_active_in asserts a site where the gene product carries out its molecular function, which is a considerably stronger claim than located_in. The objection is to the term and qualifier, not to the phylogenetic inference: a neuron-restricted site of action for a ubiquitously expressed secretory-pathway Rab is a strong statement, and the donors are a divergent fly Rab and rat Rab1a whose cell-body localization reflects where the protein was looked for. That RAB1B's IBAs are anchored at three different PANTHER nodes is normal - different functions arise at different depths in a family, and PAINT anchors each where the curator judged it to have originated - so it is not itself evidence against this annotation. What would settle it is direct evidence that RAB1B does secretory-pathway work specifically in the neuronal cell body. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG CONTEXT OR TISSUE MISMATCH Sources checked: FB:FBgn0035155 · RabX6 (Drosophila melanogaster) SOURCE WEAK OR INFERRED RabX6 is a divergent Drosophila Rab, not a Rab1 ortholog, so a neuronal localization for it is weak grounds for asserting where human RAB1B is active. RGD:619736 · Rab1a (rat) SUPPORTS SOURCE BUT NOT TARGET Rat Rab1a is a genuine ortholog of the RAB1 pair, but a cell-body localization in neurons reflects where the protein was looked for rather than a neuron-restricted function, and it does not license an is_active_in claim on the human paralog. PANTHER:PTN001178334 · PANTHER node anchoring the neuronal cell body assertion SUPPORTS SOURCE BUT NOT TARGET Anchoring this term at a different node from the gene's other IBAs is expected - different functions arise at different depths and PAINT places each where the curator judged it to have originated. The concern is the is_active_in qualifier rather than the node placement. |
| GO:0006886 intracellular protein transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Intracellular protein transport, the parent of the ER-to-Golgi term already annotated. Reason: True but general; GO:0006888 states the same claim with the compartments named. Non-core. |
| GO:0000045 autophagosome assembly | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Autophagosome assembly, propagated from yeast Ypt1 and human RAB1A. Reason: Involved_in autophagosome assembly is a stronger statement than the regulation term this gene carries from direct evidence, and RAB1B's contribution is to supply the secretory-pathway input rather than to build the phagophore. Kept as non-core rather than flagged, since yeast Ypt1 does have an established role in autophagy and the orthology is sound. |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: GTPase activity, the defining enzymatic activity of a Rab. Reason: RAB1B hydrolyses GTP, and this is what makes it a molecular switch rather than a constitutive binder. Supported by two independent EXP experiments including a structural study of the Rab-RabGAP transition state, plus IBA across the whole Rab family. Core. Supporting Evidence: PMID:23236136 Catalytic mechanism of a mammalian Rab |
| GO:0003925 G protein activity | IEA GO_REF:0000120 | ACCEPT | Summary: G protein activity, the switch behaviour of the GTPase. Reason: The GO definition of G protein activity covers small monomeric GTPases, not only heterotrimeric G proteins, and EC 3.6.5.2 is the small-GTPase entry. This is the same activity as GO:0003924 stated at the level of the switch cycle rather than the hydrolysis step. Core. |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: GTP binding, directly demonstrated. Reason: Nucleotide binding is the other half of the switch and is what the P-loop and switch regions exist for. Core. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Cytoplasm, the broadest location term, on a gene with seven specific ones. Reason: RAB1B carries ER membrane, ERGIC membrane, Golgi membrane, transport vesicle and cytosol. The bare cytoplasm parent adds nothing to any of them. The IEA copy carries UniProtKB-SubCell:SL-0086, making this an instance of the SL project's pattern A; see projects/SL.md. |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IEA GO_REF:0000117 | ACCEPT | Summary: Endoplasmic reticulum to Golgi vesicle-mediated transport. RAB1B's principal biological process. Reason: RAB1B is the Rab of the early secretory pathway, governing tethering and fusion of COPII carriers at the ERGIC and cis-Golgi. Supported here by an IGI with RAB1A, the paralog it acts redundantly with. Core. Supporting Evidence: PMID:21680502 Rab1 activity is required for anterograde transport of viral envelope proteins to post-ER compartments for virus assembly |
| GO:0007030 Golgi organization | IEA GO_REF:0000117 | ACCEPT | Summary: Golgi organization, supported by IMP in a systematic Rab knockdown screen. Reason: A genome-wide siRNA screen of human Rabs found that knocking down any one of six Golgi-resident Rabs, RAB1B among them, fragments the Golgi, and that re-expression of the respective Rab rescues it. Maintaining compact Golgi morphology is a direct consequence of sustained ER-to-Golgi flux, so this is core rather than incidental. Supporting Evidence: PMID:26209634 induced fragmentation of the Golgi in HeLa-S3 cells and that its phenotype was rescued by re-expression of their respective |
| GO:0016020 membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Bare membrane, with UniProtKB-SubCell:SL-0162 as its sole IEA source. Reason: A textbook instance of the SL project's pattern A: the generic membrane keyword propagates to a protein whose specific membranes - ER, ERGIC, Golgi - are all independently annotated. Not false, only empty. See projects/SL/SL-0162-MEMBRANE.md. |
| GO:0034045 phagophore assembly site membrane | IEA GO_REF:0000044 | MODIFY | Summary: Phagophore assembly site membrane. RAB1B is a secretory-pathway GTPase acting upstream of the phagophore, not a resident of its membrane. Reason: GO:0034045 asserts via bounding_layer_of that a membrane bounds the phagophore assembly site. The PAS is a liquid-like protein condensate with no bounding bilayer, and the term carries phagophore and isolation membrane as related synonyms of the distinct term GO:0061908 - see GO issue #29437 and projects/CONDENSATES/GO_0034045-annotation-audit.md. RAB1B differs from the other genes in that triage set. ATG9A, WIPI2, ATG16L1 and ATG12 are phagophore-membrane proteins and their assertions move to GO:0061908 or the proposed phagophore membrane term. What PMID:20545908 shows for RAB1B is that its activity, and functional ER exit sites, are required for autophagosome formation, and that the autophagic and secretory pathways intersect before the brefeldin A block - a requirement located upstream, at the ER, not a residency on the phagophore bilayer. The site-level term GO:0000407 is therefore the appropriate destination rather than a membrane term, and the functional claim is already carried by GO:2000785. The second assertion has UniProtKB-SubCell:SL-0221 as its only source, so it is also an SL propagation. Proposed replacements: phagophore assembly site Supporting Evidence: PMID:20545908 We present evidence indicating that the activity of both proteins is required for autophagosome formation. PMID:20545908 the autophagic and secretory pathways intersect at a level preceding the brefeldin A blockage |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Perinuclear region of cytoplasm, from UniProtKB-SubCell:SL-0198 alone; a restatement of Golgi position, not an additional location. Reason: The Golgi ribbon in most cultured mammalian cells sits in the perinuclear region, so a Golgi-resident protein will always appear perinuclear. SL-0221 is the only source; no experiment on this gene distinguishes a perinuclear pool from the Golgi pool. An SL-unique annotation of the kind catalogued in projects/SL.md. |
| GO:1903020 positive regulation of glycoprotein metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: Positive regulation of glycoprotein metabolic process. A metabolic reading of what is really a transport observation. Reason: The IGI comes from PMID:21680502, where the finding is that RAB1A and RAB1B together are needed for herpes simplex virus 1 envelope glycoproteins to move from the ER to the assembly compartment, where they undergo glycosylation. RAB1B does not act on the glycosylation chemistry; it delivers the substrate to the compartment that performs it, so any effect on glycoprotein metabolism is a downstream consequence of anterograde transport. GO:0006888 states this directly and is already annotated to the gene from the same experiment. Redirected there rather than left as a metabolic claim the evidence does not make. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport Supporting Evidence: PMID:21680502 Rab1 activity is required for anterograde transport of viral envelope proteins to post-ER compartments for virus assembly |
| GO:0005515 protein binding | IPI PMID:21378754 A structural basis for Lowe syndrome caused by mutations in ... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0005515 protein binding | IPI PMID:22011575 Protein LidA from Legionella is a Rab GTPase supereffector. | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0005515 protein binding | IPI PMID:25107275 A role of OCRL in clathrin-coated pit dynamics and uncoating... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0005515 protein binding | IPI PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LR... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0005515 protein binding | IPI PMID:26977884 PITPNC1 Recruits RAB1B to the Golgi Network to Drive Maligna... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0005515 protein binding | IPI PMID:31046837 Parkinson's disease-associated LRRK2-G2019S mutant acts thro... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endoplasmic reticulum-Golgi intermediate compartment, the parent of the membrane term. Reason: Less informative than GO:0033116, which this gene carries, and supported here only by an Ensembl projection from the mouse entry. Non-core. |
| GO:0005783 endoplasmic reticulum | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Endoplasmic reticulum, the parent of the ER membrane term already annotated. Reason: A prenylated peripheral membrane GTPase is on the membrane, not in the lumen, so GO:0005789 is the informative term. Non-core. |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Golgi apparatus, the parent of the Golgi membrane term already annotated. Reason: Less informative than GO:0000139, which this gene carries. Non-core. |
| GO:0003924 GTPase activity | EXP PMID:23236136 Catalytic mechanism of a mammalian Rab·RabGAP complex in ato... | ACCEPT | Summary: GTPase activity, the defining enzymatic activity of a Rab. Reason: RAB1B hydrolyses GTP, and this is what makes it a molecular switch rather than a constitutive binder. Supported by two independent EXP experiments including a structural study of the Rab-RabGAP transition state, plus IBA across the whole Rab family. Core. Supporting Evidence: PMID:23236136 Catalytic mechanism of a mammalian Rab |
| GO:0003924 GTPase activity | EXP PMID:9437002 The putative "switch 2" domain of the Ras-related GTPase, Ra... | ACCEPT | Summary: GTPase activity, the defining enzymatic activity of a Rab. Reason: RAB1B hydrolyses GTP, and this is what makes it a molecular switch rather than a constitutive binder. Supported by two independent EXP experiments including a structural study of the Rab-RabGAP transition state, plus IBA across the whole Rab family. Core. Supporting Evidence: PMID:23236136 Catalytic mechanism of a mammalian Rab |
| GO:0005737 cytoplasm | EXP PMID:11389151 Membrane targeting of a Rab GTPase that fails to associate w... | MARK AS OVER ANNOTATED | Summary: Cytoplasm, the broadest location term, on a gene with seven specific ones. Reason: RAB1B carries ER membrane, ERGIC membrane, Golgi membrane, transport vesicle and cytosol. The bare cytoplasm parent adds nothing to any of them. The IEA copy carries UniProtKB-SubCell:SL-0086, making this an instance of the SL project's pattern A; see projects/SL.md. |
| GO:0016020 membrane | EXP PMID:11389151 Membrane targeting of a Rab GTPase that fails to associate w... | MARK AS OVER ANNOTATED | Summary: Bare membrane, with UniProtKB-SubCell:SL-0162 as its sole IEA source. Reason: A textbook instance of the SL project's pattern A: the generic membrane keyword propagates to a protein whose specific membranes - ER, ERGIC, Golgi - are all independently annotated. Not false, only empty. See projects/SL/SL-0162-MEMBRANE.md. |
| GO:0003925 G protein activity | IMP PMID:20545908 Autophagosome formation depends on the small GTPase Rab1 and... | ACCEPT | Summary: G protein activity, the switch behaviour of the GTPase. Reason: The GO definition of G protein activity covers small monomeric GTPases, not only heterotrimeric G proteins, and EC 3.6.5.2 is the small-GTPase entry. This is the same activity as GO:0003924 stated at the level of the switch cycle rather than the hydrolysis step. Core. |
| GO:0007030 Golgi organization | IMP PMID:26209634 Small GTPase Rab2B and Its Specific Binding Protein Golgi-as... | ACCEPT | Summary: Golgi organization, supported by IMP in a systematic Rab knockdown screen. Reason: A genome-wide siRNA screen of human Rabs found that knocking down any one of six Golgi-resident Rabs, RAB1B among them, fragments the Golgi, and that re-expression of the respective Rab rescues it. Maintaining compact Golgi morphology is a direct consequence of sustained ER-to-Golgi flux, so this is core rather than incidental. Supporting Evidence: PMID:26209634 induced fragmentation of the Golgi in HeLa-S3 cells and that its phenotype was rescued by re-expression of their respective |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8870469 | KEEP AS NON CORE | Summary: Cytosol, the GDI-bound soluble pool of a prenylated Rab. Reason: Rab GTPases cycle between a membrane-bound active pool and a cytosolic pool held by GDI, so a cytosolic annotation is mechanistically real. It is not where the protein does its work. Non-core. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-6811423 | ACCEPT | Summary: Endoplasmic reticulum membrane, the donor compartment for the step RAB1B controls. Reason: RAB1B acts on carriers leaving ER exit sites, so ER membrane is a genuine site of action rather than a passive location. Core. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-6811427 | ACCEPT | Summary: Endoplasmic reticulum membrane, the donor compartment for the step RAB1B controls. Reason: RAB1B acts on carriers leaving ER exit sites, so ER membrane is a genuine site of action rather than a passive location. Core. |
| GO:0030133 transport vesicle | TAS Reactome:R-HSA-6807877 | KEEP AS NON CORE | Summary: Transport vesicle, from six Reactome reactions. Reason: RAB1B rides on and tethers ER-derived carriers, so the location is real. It is the cargo container rather than the compartment where the switch acts, and the ERGIC and Golgi membrane terms carry more information. Non-core. |
| GO:0030133 transport vesicle | TAS Reactome:R-HSA-6809003 | KEEP AS NON CORE | Summary: Transport vesicle, from six Reactome reactions. Reason: RAB1B rides on and tethers ER-derived carriers, so the location is real. It is the cargo container rather than the compartment where the switch acts, and the ERGIC and Golgi membrane terms carry more information. Non-core. |
| GO:0030133 transport vesicle | TAS Reactome:R-HSA-6809006 | KEEP AS NON CORE | Summary: Transport vesicle, from six Reactome reactions. Reason: RAB1B rides on and tethers ER-derived carriers, so the location is real. It is the cargo container rather than the compartment where the switch acts, and the ERGIC and Golgi membrane terms carry more information. Non-core. |
| GO:0030133 transport vesicle | TAS Reactome:R-HSA-6811418 | KEEP AS NON CORE | Summary: Transport vesicle, from six Reactome reactions. Reason: RAB1B rides on and tethers ER-derived carriers, so the location is real. It is the cargo container rather than the compartment where the switch acts, and the ERGIC and Golgi membrane terms carry more information. Non-core. |
| GO:0030133 transport vesicle | TAS Reactome:R-HSA-6811423 | KEEP AS NON CORE | Summary: Transport vesicle, from six Reactome reactions. Reason: RAB1B rides on and tethers ER-derived carriers, so the location is real. It is the cargo container rather than the compartment where the switch acts, and the ERGIC and Golgi membrane terms carry more information. Non-core. |
| GO:0030133 transport vesicle | TAS Reactome:R-HSA-6811426 | KEEP AS NON CORE | Summary: Transport vesicle, from six Reactome reactions. Reason: RAB1B rides on and tethers ER-derived carriers, so the location is real. It is the cargo container rather than the compartment where the switch acts, and the ERGIC and Golgi membrane terms carry more information. Non-core. |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-5694441 | ACCEPT | Summary: Endoplasmic reticulum-Golgi intermediate compartment membrane, from nine Reactome reactions. Reason: The ERGIC is where RAB1B is most concentrated and where it recruits its tethering effectors. Core location, though again the nine assertions are one claim counted per reaction. |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-6807864 | ACCEPT | Summary: Endoplasmic reticulum-Golgi intermediate compartment membrane, from nine Reactome reactions. Reason: The ERGIC is where RAB1B is most concentrated and where it recruits its tethering effectors. Core location, though again the nine assertions are one claim counted per reaction. |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-6807866 | ACCEPT | Summary: Endoplasmic reticulum-Golgi intermediate compartment membrane, from nine Reactome reactions. Reason: The ERGIC is where RAB1B is most concentrated and where it recruits its tethering effectors. Core location, though again the nine assertions are one claim counted per reaction. |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-6807868 | ACCEPT | Summary: Endoplasmic reticulum-Golgi intermediate compartment membrane, from nine Reactome reactions. Reason: The ERGIC is where RAB1B is most concentrated and where it recruits its tethering effectors. Core location, though again the nine assertions are one claim counted per reaction. |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-6807872 | ACCEPT | Summary: Endoplasmic reticulum-Golgi intermediate compartment membrane, from nine Reactome reactions. Reason: The ERGIC is where RAB1B is most concentrated and where it recruits its tethering effectors. Core location, though again the nine assertions are one claim counted per reaction. |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-6807875 | ACCEPT | Summary: Endoplasmic reticulum-Golgi intermediate compartment membrane, from nine Reactome reactions. Reason: The ERGIC is where RAB1B is most concentrated and where it recruits its tethering effectors. Core location, though again the nine assertions are one claim counted per reaction. |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-6807877 | ACCEPT | Summary: Endoplasmic reticulum-Golgi intermediate compartment membrane, from nine Reactome reactions. Reason: The ERGIC is where RAB1B is most concentrated and where it recruits its tethering effectors. Core location, though again the nine assertions are one claim counted per reaction. |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-6814831 | ACCEPT | Summary: Endoplasmic reticulum-Golgi intermediate compartment membrane, from nine Reactome reactions. Reason: The ERGIC is where RAB1B is most concentrated and where it recruits its tethering effectors. Core location, though again the nine assertions are one claim counted per reaction. |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-6814833 | ACCEPT | Summary: Endoplasmic reticulum-Golgi intermediate compartment membrane, from nine Reactome reactions. Reason: The ERGIC is where RAB1B is most concentrated and where it recruits its tethering effectors. Core location, though again the nine assertions are one claim counted per reaction. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8870466 | KEEP AS NON CORE | Summary: Cytosol, the GDI-bound soluble pool of a prenylated Rab. Reason: Rab GTPases cycle between a membrane-bound active pool and a cytosolic pool held by GDI, so a cytosolic annotation is mechanistically real. It is not where the protein does its work. Non-core. |
| GO:0090557 establishment of endothelial intestinal barrier | IMP NOT PMID:23885123 JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate... | UNDECIDED | Summary: NOT establishment of endothelial intestinal barrier. Two separate problems: the supporting evidence cannot be located in the cached full text, and the term names the wrong cell layer for the study it cites. Reason: On the evidence: the cached full text of PMID:23885123 runs to roughly 155 kB and mentions Rap2c some ninety times, but contains no occurrence of Rab1 or RAB1B. The annotation may rest on a supplementary screen figure not captured in the cache, and per project policy an experimental annotation is not overruled on the strength of an incomplete cache, so this is left UNDECIDED rather than removed. On the term: GO:0090557 is defined as a barrier between endothelial cell layers of the intestine, whereas PMID:23885123 is explicitly about intestinal epithelial tight junctions. GO has establishment of endothelial barrier, of skin barrier, of blood-brain barrier and of Sertoli cell barrier, but no term for the intestinal epithelial barrier, which is presumably why an endothelial term was used for an epithelial experiment. A replacement is proposed under proposed_new_terms. Resolving the evidence question needs the paper's supplementary data. Supporting Evidence: PMID:23885123 Intestinal barrier function is regulated by epithelial tight junctions |
| GO:2000785 regulation of autophagosome assembly | IMP PMID:20545908 Autophagosome formation depends on the small GTPase Rab1 and... | KEEP AS NON CORE | Summary: Regulation of autophagosome assembly, the accurate rendering of what PMID:20545908 actually demonstrates. Reason: Dominant-negative RAB1B and RAB1B siRNA both impair LC3 puncta formation and LC3-II processing, so RAB1B is genuinely required for autophagosome biogenesis. The regulation framing is right for a gene that supplies membrane and machinery through the secretory pathway rather than acting on the phagophore itself. Non-core: a downstream consequence of the ER-to-Golgi function, not a separate activity. Supporting Evidence: PMID:20545908 We present evidence indicating that the activity of both proteins is required for autophagosome formation. |
| GO:0034045 phagophore assembly site membrane | IDA PMID:20545908 Autophagosome formation depends on the small GTPase Rab1 and... | MODIFY | Summary: Phagophore assembly site membrane. RAB1B is a secretory-pathway GTPase acting upstream of the phagophore, not a resident of its membrane. Reason: GO:0034045 asserts via bounding_layer_of that a membrane bounds the phagophore assembly site. The PAS is a liquid-like protein condensate with no bounding bilayer, and the term carries phagophore and isolation membrane as related synonyms of the distinct term GO:0061908 - see GO issue #29437 and projects/CONDENSATES/GO_0034045-annotation-audit.md. RAB1B differs from the other genes in that triage set. ATG9A, WIPI2, ATG16L1 and ATG12 are phagophore-membrane proteins and their assertions move to GO:0061908 or the proposed phagophore membrane term. What PMID:20545908 shows for RAB1B is that its activity, and functional ER exit sites, are required for autophagosome formation, and that the autophagic and secretory pathways intersect before the brefeldin A block - a requirement located upstream, at the ER, not a residency on the phagophore bilayer. The site-level term GO:0000407 is therefore the appropriate destination rather than a membrane term, and the functional claim is already carried by GO:2000785. The second assertion has UniProtKB-SubCell:SL-0221 as its only source, so it is also an SL propagation. Proposed replacements: phagophore assembly site Supporting Evidence: PMID:20545908 We present evidence indicating that the activity of both proteins is required for autophagosome formation. PMID:20545908 the autophagic and secretory pathways intersect at a level preceding the brefeldin A blockage |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IGI PMID:21680502 Analysis of Rab GTPase-activating proteins indicates that Ra... | ACCEPT | Summary: Endoplasmic reticulum to Golgi vesicle-mediated transport. RAB1B's principal biological process. Reason: RAB1B is the Rab of the early secretory pathway, governing tethering and fusion of COPII carriers at the ERGIC and cis-Golgi. Supported here by an IGI with RAB1A, the paralog it acts redundantly with. Core. Supporting Evidence: PMID:21680502 Rab1 activity is required for anterograde transport of viral envelope proteins to post-ER compartments for virus assembly |
| GO:0019068 virion assembly | IMP NOT PMID:21680502 Analysis of Rab GTPase-activating proteins indicates that Ra... | ACCEPT | Summary: Virion assembly, annotated twice from one paper with opposite polarity - an IMP NOT and an IGI positive. Read together they are a correct paralog-redundancy record, not a contradiction. Reason: PMID:21680502 treats RAB1A and RAB1B as a redundant pair throughout, writing Rab1a/b, and the phenotype appears when the pair is removed. Depleting RAB1B alone gives no effect, which is what the IMP NOT|involved_in records; depleting it together with RAB1A blocks trafficking of herpes simplex virus 1 glycoproteins from the ER to the assembly compartment so that unenveloped particles accumulate, which is what the IGI with UniProtKB:P62820 records. This is exactly how GO intends genetic redundancy to be captured and it is worth preserving as a model; a curator seeing only one of the two would draw the wrong conclusion. Both retained as stated. Supporting Evidence: PMID:21680502 In the absence of Rab1a/b, the viral glycoproteins are unable to traffic from the endoplasmic reticulum to the assembly compartment, and thus unenveloped particles build up in the cytoplasm. |
| GO:0019068 virion assembly | IGI PMID:21680502 Analysis of Rab GTPase-activating proteins indicates that Ra... | ACCEPT | Summary: Virion assembly, annotated twice from one paper with opposite polarity - an IMP NOT and an IGI positive. Read together they are a correct paralog-redundancy record, not a contradiction. Reason: PMID:21680502 treats RAB1A and RAB1B as a redundant pair throughout, writing Rab1a/b, and the phenotype appears when the pair is removed. Depleting RAB1B alone gives no effect, which is what the IMP NOT|involved_in records; depleting it together with RAB1A blocks trafficking of herpes simplex virus 1 glycoproteins from the ER to the assembly compartment so that unenveloped particles accumulate, which is what the IGI with UniProtKB:P62820 records. This is exactly how GO intends genetic redundancy to be captured and it is worth preserving as a model; a curator seeing only one of the two would draw the wrong conclusion. Both retained as stated. Supporting Evidence: PMID:21680502 In the absence of Rab1a/b, the viral glycoproteins are unable to traffic from the endoplasmic reticulum to the assembly compartment, and thus unenveloped particles build up in the cytoplasm. |
| GO:1903020 positive regulation of glycoprotein metabolic process | IGI PMID:21680502 Analysis of Rab GTPase-activating proteins indicates that Ra... | MODIFY | Summary: Positive regulation of glycoprotein metabolic process. A metabolic reading of what is really a transport observation. Reason: The IGI comes from PMID:21680502, where the finding is that RAB1A and RAB1B together are needed for herpes simplex virus 1 envelope glycoproteins to move from the ER to the assembly compartment, where they undergo glycosylation. RAB1B does not act on the glycosylation chemistry; it delivers the substrate to the compartment that performs it, so any effect on glycoprotein metabolism is a downstream consequence of anterograde transport. GO:0006888 states this directly and is already annotated to the gene from the same experiment. Redirected there rather than left as a metabolic claim the evidence does not make. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport Supporting Evidence: PMID:21680502 Rab1 activity is required for anterograde transport of viral envelope proteins to post-ER compartments for virus assembly |
| GO:0005515 protein binding | IPI PMID:15796781 Identification and characterization of Iporin as a novel int... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from eleven IPI experiments; uninformative, and it is hiding the Legionella interaction. Reason: Per project curation guidance, protein binding says nothing about what the gene product does. Several of the partners here are individually informative in ways the term erases: RABIF/MSS4 is a nucleotide exchange factor, OCRL is an inositol 5-phosphatase recruited by Rab1, LRRK2 phosphorylates Rab GTPases in its switch II region and RAB1B is not the canonical LRRK2 substrate, and UniProtKB:Q5ZWZ3 is a Legionella pneumophila protein - the pathogen effector system that hijacks host Rab1 by acting as its exchange factor and AMPylating it. A host-pathogen interaction of that significance deserves better than a bare binding term. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | MARK AS OVER ANNOTATED | Summary: Extracellular exosome, from a single high-throughput proteomics dataset. Reason: RAB1B is a prenylated cytoplasmic-leaflet GTPase of the early secretory pathway with no route to the exosome lumen or surface. Detection in an exosome preparation is expected for an abundant membrane-trafficking protein and reflects the co-purification behaviour of such preparations rather than a functional location. This is one of the most frequently over-applied CC terms in the human annotation corpus. |
| GO:0005525 GTP binding | IDA PMID:20937701 Family-wide characterization of the DENN domain Rab GDP-GTP ... | ACCEPT | Summary: GTP binding, directly demonstrated. Reason: Nucleotide binding is the other half of the switch and is what the P-loop and switch regions exist for. Core. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6809006 | ACCEPT | Summary: Golgi membrane, asserted from nine Reactome reactions. Reason: The membrane RAB1B works on at the acceptor end of the ER-to-Golgi step. The nine assertions are one claim repeated once per Reactome reaction rather than nine observations, but the claim itself is a core location. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6809010 | ACCEPT | Summary: Golgi membrane, asserted from nine Reactome reactions. Reason: The membrane RAB1B works on at the acceptor end of the ER-to-Golgi step. The nine assertions are one claim repeated once per Reactome reaction rather than nine observations, but the claim itself is a core location. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6809011 | ACCEPT | Summary: Golgi membrane, asserted from nine Reactome reactions. Reason: The membrane RAB1B works on at the acceptor end of the ER-to-Golgi step. The nine assertions are one claim repeated once per Reactome reaction rather than nine observations, but the claim itself is a core location. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6811411 | ACCEPT | Summary: Golgi membrane, asserted from nine Reactome reactions. Reason: The membrane RAB1B works on at the acceptor end of the ER-to-Golgi step. The nine assertions are one claim repeated once per Reactome reaction rather than nine observations, but the claim itself is a core location. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6811412 | ACCEPT | Summary: Golgi membrane, asserted from nine Reactome reactions. Reason: The membrane RAB1B works on at the acceptor end of the ER-to-Golgi step. The nine assertions are one claim repeated once per Reactome reaction rather than nine observations, but the claim itself is a core location. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6811414 | ACCEPT | Summary: Golgi membrane, asserted from nine Reactome reactions. Reason: The membrane RAB1B works on at the acceptor end of the ER-to-Golgi step. The nine assertions are one claim repeated once per Reactome reaction rather than nine observations, but the claim itself is a core location. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6811415 | ACCEPT | Summary: Golgi membrane, asserted from nine Reactome reactions. Reason: The membrane RAB1B works on at the acceptor end of the ER-to-Golgi step. The nine assertions are one claim repeated once per Reactome reaction rather than nine observations, but the claim itself is a core location. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6811417 | ACCEPT | Summary: Golgi membrane, asserted from nine Reactome reactions. Reason: The membrane RAB1B works on at the acceptor end of the ER-to-Golgi step. The nine assertions are one claim repeated once per Reactome reaction rather than nine observations, but the claim itself is a core location. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-6811418 | ACCEPT | Summary: Golgi membrane, asserted from nine Reactome reactions. Reason: The membrane RAB1B works on at the acceptor end of the ER-to-Golgi step. The nine assertions are one claim repeated once per Reactome reaction rather than nine observations, but the claim itself is a core location. |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000054 | KEEP AS NON CORE | Summary: Golgi apparatus, the parent of the Golgi membrane term already annotated. Reason: Less informative than GO:0000139, which this gene carries. Non-core. |
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Download this section (compressed HTML)Q: The GO:0090557 NOT annotation cites PMID:23885123, whose cached full text does not mention Rab1 anywhere. Does the supporting evidence sit in supplementary data, and if so which figure? A negative annotation is only useful if its basis can be traced.
Q: RAB1B and RAB1A are functionally redundant, and PMID:21680502 records this correctly with a paired IMP NOT and IGI on the same term. How many other RAB1B annotations transferred from RAB1A would fail a single-knockdown test, and should redundant paralog pairs be annotated as a unit?
Q: Legionella pneumophila DrrA/SidM acts as a RAB1 exchange factor and AMPylates the switch II region. Should host proteins targeted this way carry a molecular function annotation reflecting that they are substrates of pathogen effectors, or is that properly the pathogen's annotation?
Q: RAB1B's IBAs are anchored at three PANTHER nodes for different aspects (PTN001292747, PTN000634320, PTN001178334), which is the expected PAINT pattern. But the neuronal cell body assertion carries is_active_in rather than located_in. Is that qualifier warranted for a housekeeping secretory-pathway Rab, and how does PAINT decide between the two when the descendant evidence is localization?
Experiment: Single versus double knockdown of RAB1A and RAB1B across the phenotypes currently annotated to RAB1B alone - Golgi morphology, ER-to-Golgi cargo transport, autophagosome formation - to establish which are genuinely RAB1B-specific and which require loss of the redundant pair, and so which annotations should carry IGI rather than IMP.
Experiment: Live imaging of endogenously tagged RAB1B during starvation-induced autophagy, scoring whether it is ever detected on LC3-positive phagophore membranes or only at ER exit sites upstream. This directly tests the reading proposed here, that the GO:0034045 annotation reflects an upstream requirement rather than residency on the phagophore.
Experiment: Immunoprecipitation of RAB1B from intestinal epithelial monolayers with and without JAM-A knockdown, together with transepithelial resistance measurement after RAB1B knockdown, to resolve whether the negative barrier annotation is supported and to supply evidence for the proposed epithelial barrier term.
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