FHAD1

Model summary

A human centrosome-associated scaffold that combines an N-terminal phospho-recognition module with a large coiled-coil body to assemble signaling and structural complexes. By binding phosphorylated partners and oligomerizing into higher-order assemblies, it coordinates centrosomal architecture with transcriptional programs that drive the G1/S transition. This coupling of a phospho-sensing head and a coiled-coil tail enables regulated protein interactions that promote RNA polymerase II–dependent transcription while positioning the complex at the centrosome.

Predicted Gene Ontology terms

1. 01

   I begin with the domain architecture.

   The N-terminus carries IPR008984 (SMAD/FHA domain superfamily, residues 11–95), within which sits a well-defined IPR000253 FHA domain (residues 17–85). FHA modules are phosphothreonine-recognition folds that create regulated protein–protein interfaces, typically wiring checkpoint and cell-cycle signaling. The C-terminal half is dominated by IPR060375 (CCDC27/FHAD1, coiled-coil, residues 278–537), a predicted oligomerization scaffold that stabilizes higher-order assemblies. The entire polypeptide is encompassed by IPR052642 (Coiled-coil and Forkhead-associated domain-containing protein family, residues 1–563), indicating a conserved bipartite design: an N-terminal phospho-sensor FHA domain followed by an extended coiled-coil tail that mediates multivalent assembly. This architecture causally enforces protein-binding capacity through two complementary surfaces—an FHA phospho-reader and a coiled-coil oligomerization platform—supporting GO:0005515 protein binding as the molecular function.

2. 02

   From this molecular scaffold, I infer process-level roles.

   FHA domains frequently gate cell-cycle transitions by decoding phosphorylation at centrosomes and kinetochores. The presence of a long coiled-coil region suggests a structural hub that recruits and stabilizes pericentriolar complexes. Such assemblies are well-suited to coordinate transcriptional regulators that drive entry into S phase. This mechanistic coupling explains participation in GO:0000083 regulation of transcription involved in G1/S transition of the mitotic cell cycle and GO:0045944 positive regulation of transcription by RNA polymerase II: the FHA domain senses phosphorylation cues, while the coiled-coil tail nucleates assemblies that potentiate transcriptional programs necessary for G1/S.

3. 03

   Cellular localization follows directly from the assembly logic.

   A phospho-sensing FHA head tethered to a large coiled-coil body is optimized for pericentriolar matrix scaffolding and cell-cycle signaling nodes. This predicts residence at the GO:0005813 centrosome, consistent with a role in organizing microtubule-organizing centers and coordinating mitotic entry.

4. 04

   Mechanistically, I hypothesize that the FHA domain captures phosphorylated partners during cell-cycle transitions, while the coiled-coil region oligomerizes to build a centrosomal scaffold that both senses and transmits checkpoint signals.

   This scaffold likely recruits centrosomal organizers and transcriptional regulators to synchronize structural cell-cycle events with gene expression. Likely partners include centrosomal matrix proteins and checkpoint kinases that provide phospho-motifs for FHA engagement, as well as transcriptional coactivators that amplify RNA polymerase II–driven programs at the G1/S boundary.