The invention provides methods and compositions relating to a novel kinase designated PAS Kinase (PASK). The compositions include isolated polypeptides comprising a native PASK protein or a PASK N-terminal domain and polypeptides consisting of a PASK PAS-A or PAS-B domain, as well as isolated polynucleotides encoding such polypeptides, and expression vectors and cells comprising such polynucleotides. The methods include binding assays comprising the steps of incubating a mixture comprising a subject polypeptide with a ligand under conditions wherein the polypeptide binds the ligand; and detecting binding of the polypeptide to the ligand.