Affinage mechanistic annotation for AGFG1 (human) Affinage Affinage (Claude Sonnet reading pass + Opus synthesis pass) 2 citations

Affinage mechanistic annotation for AGFG1 (human)

Current model (mechanistic narrative)

AGFG1 (HRB) is a nucleocytoplasmic adaptor protein that links the clathrin-dependent endocytic machinery to nucleocytoplasmic transport [PMID:18819912, PMID:10613896]. In the cytoplasm it colocalizes with clathrin-, AP-2-, EPS15-, and transferrin receptor-containing vesicles and binds the vesicular SNARE TI-VAMP (VAMP7); its depletion strongly reduces endocytosis of transferrin and TI-VAMP, establishing it as a required component of clathrin-dependent endocytosis PMID:18819912. AGFG1 also associates with the EH-domain proteins Eps15 and Eps15R through its EH-binding motifs, an interaction that occurs in the cytoplasm and that synergizes with AGFG1 to enhance Rev-mediated nuclear export PMID:10613896. Beyond these endocytic and Rev-export roles, no further mechanistic detail has been characterized in the available corpus.

Affinage mechanism profile (its own GO/Reactome grounding)

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.

Dated findings (citation-anchored)

Year Confidence Finding PMIDs Journal
2008 High HRB (AGFG1) was identified as a binding partner of the vesicular SNARE TI-VAMP (VAMP7) by yeast two-hybrid screening and confirmed by biochemical assays. In HeLa cells, HRB localized to the nucleus and cytoplasm, with cytoplasmic HRB colocalizing with clathrin-, AP-2-, EPS15-, and transferrin receptor-containing vesicles. Knockdown of HRB strongly reduced endocytosis of fluorescent transferrin and pHLuorin-TI-VAMP as measured by FACS, establishing HRB as a required component of clathrin-dependent endocytosis. PMID:18819912 The Journal of biological chemistry
1999 Medium HRB (AGFG1) interacts with the EH (Eps15 homology) domain-containing proteins Eps15 and Eps15R via its EH-binding motifs, and this interaction occurs in the cytoplasm. Eps15 and Eps15R synergize with HRB to enhance Rev-mediated nuclear export function, and the EH-mediated Eps15–HRB interaction is required for this synergistic effect, connecting the endocytic molecular machinery to nucleocytoplasmic transport. PMID:10613896 The Journal of cell biology

Citations