AGFG2 (HRBL) is a nucleoporin-related adaptor protein that links the endocytic machinery to nucleocytoplasmic transport and functions as a cellular co-factor in HIV-1 biology [PMID:10613896, PMID:26701340]. In the cytoplasm it binds the EH-domain proteins Eps15 and Eps15R, and this interaction is required for the synergistic enhancement of HIV-1 Rev-mediated nuclear export of viral RNAs, coupling endocytic adaptor proteins to the Rev export pathway PMID:10613896. AGFG2 also acts at the plasma membrane and early endosomes to promote HIV-1-mediated CD4 downregulation: its knockdown raises CD4 surface levels in infected T cells PMID:25496667, and pathway dissection establishes that AGFG2 serves as a co-factor for both Nef- and Vpu-mediated CD4 downregulation, distinguishing it from the paralog AGFG1/HRB, which supports only the Nef-dependent route PMID:26701340. Beyond its role as an EH-protein-binding adaptor in these HIV-1 co-factor activities, no further enzymatic or structural mechanism for AGFG2 has been characterized in the available corpus.
Recorded for reference. The AIGR evaluation found this grounding is coarse (collapses to general parents) and can contradict the narrative — do not import these GO ids directly; re-ground from the narrative + PMIDs.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 1999 | Medium | AGFG2 (Hrbl) binds to EH (Eps15 homology) domain-containing proteins Eps15 and Eps15R in the cytoplasm; this EH-mediated interaction is required for synergistic enhancement of HIV-1 Rev-mediated nuclear export of RNAs, connecting the endocytic machinery to the nucleocytoplasmic transport (Rev export) pathway. | PMID:10613896 | The Journal of cell biology |
| 2014 | Medium | Knockdown of AGFG2 (HRBL) by shRNA significantly increases CD4 surface levels in HIV-1-infected T cells, identifying AGFG2 as a cellular co-factor for HIV-1-mediated CD4 downregulation at the level of the plasma membrane and early endosomes. | PMID:25496667 | Retrovirology |
| 2015 | Medium | AGFG2 (HRBL) knockdown increases CD4 surface levels specifically in HIV-1 Vpu-expressing cells but not in Nef-expressing cells, distinguishing AGFG2's role from the related protein HRB (AGFG1), which acts as a co-factor for Nef-mediated (but not Vpu-mediated) CD4 downregulation. This identifies AGFG2 as a co-factor for both HIV-1 Nef- and Vpu-mediated CD4 downregulation. | PMID:26701340 | The Journal of general virology |
| 2011 | Low | AGFG2 molecules are present in mammals only and emerged later in evolution, likely from a duplication of AGFG1. AGFG2 contains an additional module of ~50 coding nucleotides ahead of the conserved core module (which encodes nucleoporin-related Arf-GAP domain and FG repeats), and this additional module is less conserved than the core (54% vs 67% identity from Drosophila to primates for AGFG1). | PMID:21284487 | Immunopharmacology and immunotoxicology |