Molecular cloning, structural analysis, and expression of a human IRLB, MYC promoter-binding protein: new DENN domain-containing protein family emerges

Genomics. 2003 Sep;82(3):343-54. doi: 10.1016/s0888-7543(03)00103-4.


IRLB was originally identified as a partial cDNA clone, encoding a 191-aa protein binding the interferon-stimulated response element (ISRE) in the P2 promoter of human MYC. Here, we cloned the full-size IRLB using different bioinformatics tools and an RT-PCR approach. The full-size gene encompasses 131 kb within chromosome 15q22 and consists of 32 exons. IRLB is transcribed as a 6.6-kb mRNA encoding a protein of 1865 aa. IRLB is ubiquitously expressed and its expression is regulated in a growth- and cell cycle-dependent manner. In addition to the ISRE-binding domain IRLB contains a tripartite DENN domain, a nuclear localization signal, two PPRs, and a calmodulin-binding domain. The presence of DENN domains predicts possible interactions of IRLB with GTPases from the Rab family or regulation of growth-induced MAPKs. Strongly homologous proteins were identified in all available vertebrate genomes as well as in Caenorhabditis elegans and Drosophila melanogaster. In human and mouse a family of IRLB proteins exists, consisting of at least three members.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA, Complementary
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Death Domain Receptor Signaling Adaptor Proteins
  • Fibroblasts
  • Guanine Nucleotide Exchange Factors / genetics*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA
  • Sequence Analysis, Protein


  • DENND4A protein, human
  • DNA, Complementary
  • DNA-Binding Proteins
  • Death Domain Receptor Signaling Adaptor Proteins
  • Guanine Nucleotide Exchange Factors
  • MADD protein, human
  • Madd protein, mouse
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger

Associated data

  • GENBANK/AF534403