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FHIP2A

FHF complex subunit HOOK interacting protein 2A · UniProt Q5W0V3

Length
765 aa
Mass
86.6 kDa
Annotated
2026-06-09
7 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FHIP2A is an adaptor subunit that couples cytoplasmic dynein-1 to ER-to-Golgi membrane cargo, functioning as part of an FTS-Hook2-FHIP2A (FHF) complex that associates with Rab1A-marked ER-to-Golgi cargos and drives the motility of Rab1A tubules (PMID:34882091). FHIP2A engages the small GTPase Rab1 (Rab1A/Rab1B) in a strictly membrane-dependent manner, and this interaction recruits dynein to the ER-Golgi intermediate compartment (ERGIC), establishing the molecular link between a membrane-bound Rab GTPase and the dynein transport machinery (PMID:41493270). Beyond its role as a Rab1-dependent dynein adaptor in ER-to-Golgi transport, no further mechanistic detail has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2021 High

    Established that FHIP2A is a constituent of the FHF complex that physically links dynein-1 to ER-to-Golgi cargo, answering how this transport machinery couples to its membrane cargo and identifying Rab1A tubules as the cargo whose motility it controls.

    Evidence Proteomic interactome mapping, live-cell imaging, and single-molecule in vitro reconstitution

    PMID:34882091

    Open questions at the time
    • Direct molecular contact between FHIP2A and the cargo was not resolved
    • Mechanism of dynein activation by the complex not detailed at residue level
  2. 2026 High

    Resolved how FHIP2A connects to cargo by showing it binds Rab1 only in the presence of membranes, explaining why the interaction was missed by conventional assays and defining the ERGIC as the site of dynein recruitment.

    Evidence MitoID proximity biotinylation interactome with in vitro binding validation and a membrane-dependent interaction assay

    PMID:41493270

    Open questions at the time
    • Structural basis of the membrane-dependent Rab1-FHIP2A interface unknown
    • Whether GTP/GDP state of Rab1 alone is sufficient versus additional membrane lipid requirements not fully dissected
    • Functional consequences of disrupting the interaction in vivo not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FHIP2A-mediated dynein recruitment is regulated and integrated with other ER-to-Golgi trafficking events remains unresolved.
  • No structure of the FHF-Rab1-membrane assembly
  • Regulatory inputs controlling FHIP2A engagement unknown
  • Tissue/physiological roles not addressed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 2
Partners
DYNC1H1FTSHOOK2RAB1ARAB1B
Complex memberships
FHF complex (FTS-Hook2-FHIP2A)

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 FHIP2A forms a FTS-Hook2-FHIP2A complex (FHF complex) that associates with Rab1A-tagged ER-to-Golgi cargos and is involved in the motility of Rab1A tubules, linking cytoplasmic dynein-1 to ER-to-Golgi cargo transport. Proteomic interactome mapping, live-cell imaging, biochemical co-purification, single-molecule in vitro reconstitution assays eLife High 34882091
2026 FHIP2A interacts with the small GTPase Rab1 (Rab1A/Rab1B) in a membrane-dependent manner, and this interaction recruits dynein to the ER-Golgi intermediate compartment (ERGIC); the interaction could only be detected in the presence of membranes, explaining why it was missed by conventional methods. MitoID proximity biotinylation interactome, in vitro binding validation, membrane-dependent interaction assay The Journal of cell biology High 41493270

Source papers

Stage 0 corpus · 7 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield. Molecular psychiatry 202 27431290
2021 Cytoplasmic dynein-1 cargo diversity is mediated by the combinatorial assembly of FTS-Hook-FHIP complexes. eLife 37 34882091
2017 A Genome-wide Expression Association Analysis Identifies Genes and Pathways Associated with Amyotrophic Lateral Sclerosis. Cellular and molecular neurobiology 29 28639078
2015 A susceptibility locus rs7099208 is associated with non-obstructive azoospermia via reduction in the expression of FAM160B1. Journal of biomedical research 3 26668583
2019 FAM160B1 deficit associated with microcephaly, severe intellectual disability, ataxia, behavioral abnormalities and speech problems. Clinical genetics 2 31353455
2026 A Rab1 interactome illuminates a dual role in autophagy and membrane trafficking. The Journal of cell biology 1 41493270
2015 Erratum: A susceptibility locus rs7099208 is associated with non-obstructive azoospermia via reduction in the expression of FAM160B1. Journal of biomedical research 0 26673547

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