A hepatitis-C-associated microtubular aggregate protein, referred to as p44, has been identified as a cytoplasmic antigen in the hepatocytes of chimpanzees infected with hepatitis C virus. The production of p44 mRNA is markedly induced in the liver of chimpanzees infected with hepatitis C or hepatitis D virus. To examine the mechanism of this induction, we isolated a genomic clone for the human p44 protein and analyzed its structure. The human p44 gene spans approximately 14 kbp of DNA and consists of nine exons separated by eight introns. An interferon-stimulated response element, which confers inducibility by interferon-alpha/beta, was found in the promoter region of the gene. Northern-blot analysis revealed that the human p44 gene is inducible by interferon-alpha/beta, but not by interferon-gamma. Functional analysis demonstrated that the interferon-stimulated response element in the promoter region of the gene mediates the inducibility of the gene by interferon-alpha/beta. Thus, the human p44 gene is a member of the family of interferon-alpha/beta inducible genes. The protein p44 may be one of the mediators involved in the antiviral action of interferon.