FAM161B

FAM161B is a microtubule-associated protein that interacts with FAM161A through the conserved UPF0564 domain, which also mediates direct microtubule binding (PMID:22791751). FAM161B is part of a centrosome-associated protein network, physically interacting with the mitotic spindle regulator TACC3 (PMID:20237422). Studies of the Drosophila orthologue (Fam161, orthologous to both FAM161A and FAM161B) demonstrate that this protein family localizes to centrioles and the cilium transition zone and is essential for male reproduction and sensory-dependent behavior, establishing a conserved role in centriole and ciliary function (PMID:39255847).

1. 2010 Low

   Placing FAM161B within a centrosome-associated complex: an interactome screen identified FAM161B as a physical interactor of TACC3, linking FAM161B for the first time to centrosome biology and cell division.

   Evidence Co-purification/pull-down from a TACC3-centered interactome mapping in human cells

   PMID:20237422

   Open questions at the time

   • Single interactome hit without reciprocal validation or mechanistic follow-up on FAM161B
   • No functional characterization of FAM161B's role at the centrosome
   • Interaction stoichiometry and directness not established
2. 2012 Medium

   Defining the molecular basis of the FAM161A–FAM161B interaction and connecting both proteins to microtubules: the conserved UPF0564 domain was shown to mediate heterotypic binding between FAM161A and FAM161B as well as direct microtubule association, establishing a shared structural platform for cytoskeletal engagement.

   Evidence Pull-down and co-immunoprecipitation with domain deletion/mutagenesis in cultured mammalian cells

   PMID:22791751

   Open questions at the time

   • Functional consequence of the FAM161A–FAM161B interaction in cells was not tested (e.g., by co-depletion)
   • No structural data on the UPF0564 domain or the interaction interface
   • Endogenous complex stoichiometry and tissue-specific relevance remain undefined
3. 2024 Medium

   Establishing in vivo essentiality for centriole and cilium transition zone function: loss-of-function of the Drosophila FAM161A/B orthologue demonstrated that this protein family is required for ciliary integrity, male fertility, and geotaxis behavior, grounding the biochemical observations in an organismal context.

   Evidence Genetic knockout, immunofluorescence localization to centrioles and transition zone, and behavioral/reproductive phenotyping in Drosophila

   PMID:39255847

   Open questions at the time

   • Drosophila has a single orthologue for both FAM161A and FAM161B, so individual contributions of mammalian paralogues remain unresolved
   • No mammalian loss-of-function data for FAM161B specifically
   • Mechanism by which FAM161B contributes to transition zone assembly or ciliary gating is unknown

• The specific, non-redundant functions of FAM161B versus FAM161A in mammalian cells — including whether FAM161B is required for ciliogenesis, centrosome integrity, or cell division — remain uncharacterized by direct mammalian genetic or functional studies.
• No mammalian knockout or knockdown phenotype reported for FAM161B
• No disease association established for FAM161B mutations (unlike FAM161A in retinitis pigmentosa)
• Structural basis for UPF0564-mediated microtubule binding and partner selectivity is unknown