Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module.
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The paper in which the AGFG2 cDNA (as RAB-R) was isolated, and, according to the later PMID:10613896, one of the two original reports that EH-domain proteins interact with Hrbl. The cached record is abstract-only and the abstract names RAB (AGFG1) but not RAB-R, so the AGFG2-specific claim cannot be checked here.
The eps15 homology (EH) domain-based interaction between eps15 and hrb connects the molecular machinery of endocytosis to that of nucleocytosolic transport.
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Overexpressed Hrbl (AGFG2) increased Rev-dependent reporter activity by about 50%, the same as Hrb, and synergised with Eps15 or Eps15R to give a 3.0-3.5-fold increase; co-expression of Eps15 with either Hrb or Hrbl raised steady-state Rev levels four- to sixfold.
"A synergistic effect of coexpressing Eps15 or Eps15R with either Hrb or Hrbl, was readily observable (Fig."
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The colocalisation and subcellular-fractionation experiments in this paper were done on Hrb, not on Hrbl. The anti-Hrbl serum was used to confirm expression levels, so the punctate extranuclear structures shared with Eps15 are a result about AGFG1. This is why the paper's GO:0031410 EXP annotation sits on AGFG1 and not on AGFG2.
"We determined colocalization of Eps15 and Hrb by confocal microscopy."
Lack of acrosome formation in Hrb-deficient mice.
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Mouse Hrb-null spermatids form proacrosomal vesicles that fail to fuse, supporting an active role in acrosome assembly and providing descendant evidence for the ancestral IBD.
"Although proacrosomic vesicles form in spermatids that lack Hrb, the vesicles are unable to fuse, blocking acrosome development at step 2."
The acroplaxome is the docking site of Golgi-derived myosin Va/Rab27a/b- containing proacrosomal vesicles in wild-type and Hrb mutant mouse spermatids.
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Mouse Hrb-null spermatids have a keratin-5-deficient acroplaxome and altered nuclear shaping, linking vesicle traffic to cytoskeletal organization.
"Yet the acroplaxome in the mutant contains F-actin but is deficient in keratin 5."
Changes in intranuclear chromatin architecture induce bipolar nuclear localization of histone variant H1T2 in male haploid spermatids.
Defining the membrane proteome of NK cells.
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NK-like YTS membrane proteomics identifies proteins including transiently associated species; the curated AGFG2 HDA supports broad membrane association.
"The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes."
Organization patterns of the AGFG genes: an evolutionary study.
Ancient complexity, opisthokont plasticity, and discovery of the 11th subfamily of Arf GAP proteins.
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Most AGFG sequences lack the ASAP3 Asp484-homologous residue, contributing to a prediction of reduced activity. This is not a direct AGFG assay, and active GIT proteins provide an exception to a universal Asp requirement.
"Only two of the 40 AGFG sequences contain an aspartate at the position homologous to D47 in the other subfamilies (D484 in ASAP3 structure)"
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Notes that the catalytic arginine, although highly conserved across Arf GAPs, fell just short of the study's conservation cut-off in AGFG, and that nine of the forty AGFG sequences lack it altogether. Human AGFG2 is not among those nine: it retains the arginine at position 75.
"nine of the 40 AGFG sequences lack the catalytic arginine and would be expected to be incapable of supporting robust GTP hydrolysis, even if binding to Arf is conserved."
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Independently establishes that AGFG is one of four Arf GAP subfamilies that underwent a single duplication producing two paralogues, which is the phylogenetic basis for treating AGFG1 and AGFG2 as paralogues rather than assuming it from the shared name.
"four of the subfamilies (SMAP (Figure S3G), ArfGAP2/3 (Figure S3H), AGFG (Figure S3I) and GIT (Figure 5B)) have each undergone a single duplication resulting in two paralogs"
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The same sequence survey reports loss of the Asp-homologous position in all 18 GIT sequences analyzed.
"In fact, it is absent from all 18 GIT sequences used in our analyses."
Genome-wide shRNA screening identifies host factors involved in early endocytic events for HIV-1-induced CD4 down-regulation.
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AGFG2 (HRBL) is one of seven validated hits whose knockdown significantly rescues CD4 surface expression in HIV-1-infected SupT1 cells, confirmed in a second cell background and with Nef expressed alone. Its knockdown did not significantly affect HIV-1 replication.
"Remarkably, only cells knocked down for HRBL, EPS15 and HSP90B1 were found to significantly express higher CD4 surface levels than the non-targeting shRNA control cells."
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The authors describe AGFG2 as poorly characterised and note that the transferrin endocytosis result they cite belongs to the paralogue HRB, not to HRBL - a distinction worth preserving, since it is the kind of attribution that migrates between paralogues.
"HRBL is a poorly characterized protein, but shares similarity with another Rev binding protein, HRB (HIV Rev Binding protein), which is able to affect endocytosis of transferrin in an EPS15-dependent manner"
The human immunodeficiency virus (HIV) Rev-binding protein (HRB) is a co-factor for HIV-1 Nef-mediated CD4 downregulation.
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Knockdown of HRBL (AGFG2), but not of EPS15, significantly raises CD4 levels in Vpu-expressing cells, so AGFG2 acts as a cofactor for both Nef- and Vpu-mediated CD4 downregulation, whereas AGFG1/HRB supports only the Nef route. This is the sharpest published functional distinction between the two paralogues.
"These results identify HRB as a previously unknown co-factor for HIV-1 Nef-mediated CD4 downregulation and highlight differences with the related protein HRBL, which affects the CD4 downregulation in a dual role as co-factor of both HIV-1 Nef and Vpu."
The temporally controlled expression of Drongo, the fruit fly homolog of AGFG1, is achieved in female germline cells via P-bodies and its localization requires functional Rab11.
Arf GTPase-activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor.
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siRNA depletion of AGFG2 in HUVECs halves PMA-stimulated and significantly reduces histamine-stimulated von Willebrand factor secretion, while unstimulated secretion is unchanged; overexpression of siRNA-resistant AGFG2 rescues the knockdown and drives granule release even without a secretagogue. This is the strongest evidence of function for this gene and it has produced no GO annotation.
"These results suggest that AGFG2 plays an important role in the stimulation-dependent secretion of vWF."
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AGFG2 depletion largely preserves WPB cargo delivery and morphology while reducing secretion. Quantitative changes in high-molecular-weight secreted VWF and propeptide cleavage are present, so the data favor but do not isolate a late release mechanism.
"Overall, these results indicate that vWF transport to WPBs is not highly perturbed in SMAP1KD and AGFG2KD cells."
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The paper notes the retained ArfGAP consensus and uses an R75Q construct. Its GAP-dead label is not supported by a direct AGFG2 hydrolysis measurement in this study.
"AGFG proteins were reported to lose important amino acids in ArfGAP domain (Schlacht et al., 2013), but human AGFG2 conserves ArfGAP consensus sequence CX2CX16CX2CX4R in ArfGAP domain."
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Reports that the R75Q mutant still induced vWF secretion with no detected difference from wild type, but as data not shown. This tests whether that one residue is required for that one function; it is not a measurement of GAP activity, and the authors state that the contributions of the FG repeats and the ArfGAP domain remain to be addressed.
"AGFG2[R75Q] expression also induced secretion of vWF and we have not detected the specific effects of AGFG2[R75Q] expression compared with that of wild-type AGFG2 so far (data not shown)."
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AGFG2 is enriched in salivary gland, consistent with secretory roles; enrichment does not exclude a germ-cell role.
"According to the NCBI Gene database, AGFG2 is highly expressed in salivary gland (Fagerberg et al., 2014)."
AGFG2 primary, PAINT and ontology scope check (2026-09-20)
AGFG2 reproducible bioinformatics results
Affinage mechanistic annotation for AGFG2 (human)
GIT proteins, A novel family of phosphatidylinositol 3,4, 5-trisphosphate-stimulated GTPase-activating proteins for ARF6.
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GIT1 and GIT2 have measured ARF6 GAP activity.
"Unlike ARF-GAP1, GIT1 and GIT2 stimulate hydrolysis of GTP bound to ARF6."
The structure of an Arf-ArfGAP complex reveals a Ca2+ regulatory mechanism.