Family with sequence similarity 83 member G (FAM83G)

FAM83G (PAWS1) is a member of the FAM83 protein family distinguished by the conserved DUF1669 domain. It acts as an intracellular scaffold, modulating key signaling pathways. Originally identified as a SMAD1 interactor, it mediates non-canonical BMP signaling and is phosphorylated by type I BMP receptor kinases. FAM83G controls the expression of some BMP target genes independently of canonical SMAD4 activity, and has additional roles in Wnt/β-catenin signaling by anchoring CK1 isoforms, supporting β-catenin nuclear accumulation, and driving Wnt-dependent gene transcription. Loss-of-function mutations cause defects in actin cytoskeletal regulation and cell migration, and are associated with hereditary keratoderma and abnormal hair development in humans and animals. FAM83G is not a classical receptor, enzyme, or transporter, but is notable for its cellular regulatory roles and disease relevance. Not an enzyme, transporter, or receptor; best classified as a scaffolding/signaling cofactor protein. Experimental evidence favors a role in cytoskeletal dynamics, embryogenesis, and cutaneous biology, not as a direct drug target. Human pathogenic mutations (A34E, others) disrupt associations with CK1 and attenuate canonical Wnt signaling. FAM83G/PAWS1 is a conserved scaffolding/signaling protein that interacts with SMAD1 and CK1 isoforms to regulate non-canonical BMP and canonical Wnt signaling. It is not currently considered a direct therapeutic target, but mutations cause skin and hair pathology, providing a model for understanding related signaling networks.

Other names

Protein associated with SMAD1 (PAWS1)FLJ41564PAWS1protein FAM83G

Not applicable; no drugs are currently described as acting via FAM83G.