FAM161B

FAM161B is a conserved component of the centriole and ciliary apparatus, inferred from its paralog relationship and orthologue function within the FAM161 family (PMID:22791751, PMID:39255847). It engages its paralog FAM161A through the evolutionarily conserved UPF0564 domain, which mediates both homo- and heterotypic binding among FAM161 family members (PMID:22791751). The sole Drosophila orthologue of the FAM161A/FAM161B pair localizes to centrioles and the cilium transition zone in a cell type-specific manner, and its loss impairs male reproduction and geotaxis, establishing the family as essential centriole and transition zone proteins required for cilium integrity (PMID:39255847). Beyond these interaction and orthologue-based findings, no FAM161B-specific molecular activity, substrate, or direct ciliary mechanism has been characterized in the available corpus.

1. 2010 Low

   Before any function was assigned, it was unknown what proteins FAM161B associates with; an interactome screen placed it in the orbit of the centrosomal/spindle regulator TACC3, providing the first hint of a centriole-associated role.

   Evidence TACC3 interactome mapping protein interaction screen

   PMID:20237422

   Open questions at the time

   • Single interactome screen with no reciprocal or functional validation specific to FAM161B
   • Biological consequence of the TACC3 association untested
   • Does not establish direct binding versus complex co-membership
2. 2012 Medium

   The basis for FAM161 family self-association was unknown; binding assays showed the conserved UPF0564 domain mediates homo- and heterotypic interaction between FAM161A and FAM161B, defining FAM161B as a paralog-interacting partner.

   Evidence Pull-down, yeast two-hybrid, and co-immunoprecipitation in cultured cells and retinal extracts

   PMID:22791751

   Open questions at the time

   • Functional consequence of the FAM161A–FAM161B interaction not defined
   • FAM161B-specific subcellular localization in mammalian cells not resolved
   • Stoichiometry and structural detail of the UPF0564 interface unknown
3. 2024 Medium

   Whether the FAM161 family is functionally essential at cilia was unresolved; loss-of-function in the single Drosophila orthologue localized the protein to centrioles and the transition zone and produced reproductive and behavioral defects, establishing the family as essential for cilium integrity.

   Evidence Drosophila loss-of-function mutant analysis with immunofluorescence localization across cell types

   PMID:39255847

   Open questions at the time

   • Fly orthologue covers both FAM161A and FAM161B, so FAM161B-specific contribution cannot be separated
   • Mammalian FAM161B loss-of-function phenotype not established
   • Molecular activity at the transition zone not defined

• The FAM161B-specific molecular function, its mammalian ciliary localization, and the functional role of its interactions with FAM161A and TACC3 remain undetermined.
• No FAM161B-specific catalytic or structural activity identified
• No mammalian knockout or disease association established in the corpus
• Distinct roles of FAM161B versus FAM161A not disentangled